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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Carnitine Palmitoyltransferase 1A Deficiency - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Carnitine Palmitoyltransferase 1A Deficiency">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2025/02/20">
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<meta name="citation_author" content="Kristen Lee">
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<meta name="citation_author" content="Amanda Pritchard">
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<meta name="citation_author" content="Ayesha Ahmad">
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<meta name="citation_keywords" content="CPT1A Deficiency">
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<meta name="citation_keywords" content="Hepatic Carnitine Palmitoyltransferase 1 Deficiency">
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<meta name="citation_keywords" content="CPT1A Deficiency">
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<meta name="citation_keywords" content="Hepatic Carnitine Palmitoyltransferase 1 Deficiency">
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<meta name="citation_keywords" content="Carnitine O-palmitoyltransferase 1, liver isoform">
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<meta name="citation_keywords" content="CPT1A">
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<meta name="citation_keywords" content="Carnitine Palmitoyltransferase 1A Deficiency">
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<meta name="DC.Title" content="Carnitine Palmitoyltransferase 1A Deficiency">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Kristen Lee">
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<meta name="DC.Contributor" content="Amanda Pritchard">
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<meta name="DC.Contributor" content="Ayesha Ahmad">
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<meta name="DC.Date" content="2025/02/20">
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<meta name="description" content="Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a disorder of long-chain fatty acid oxidation. Clinical manifestations usually occur in an individual with a concurrent febrile or gastrointestinal illness when energy demands are increased; onset of manifestations are usually rapid. The recognized presentations are: (1) out-of-range newborn screen (individual may be without features or with hepatic encephalopathy, hypoketotic hypoglycemia, and sudden onset of liver failure) and (2) later-onset manifestations (in the absence of newborn screening), including hepatic encephalopathy, hypoglycemia, absent or low levels of ketones, and elevated serum concentrations of liver transaminases, ammonia, and creatine kinase. Between episodes of hepatic encephalopathy, individuals appear developmentally and cognitively normal unless previous metabolic decompensation has resulted in neurologic damage. Acute fatty liver of pregnancy, in which the fetus has biallelic pathogenic variants in CPT1A, has been rarely associated with CPT1A deficiency.">
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<meta name="og:description" content="Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a disorder of long-chain fatty acid oxidation. Clinical manifestations usually occur in an individual with a concurrent febrile or gastrointestinal illness when energy demands are increased; onset of manifestations are usually rapid. The recognized presentations are: (1) out-of-range newborn screen (individual may be without features or with hepatic encephalopathy, hypoketotic hypoglycemia, and sudden onset of liver failure) and (2) later-onset manifestations (in the absence of newborn screening), including hepatic encephalopathy, hypoglycemia, absent or low levels of ketones, and elevated serum concentrations of liver transaminases, ammonia, and creatine kinase. Between episodes of hepatic encephalopathy, individuals appear developmentally and cognitively normal unless previous metabolic decompensation has resulted in neurologic damage. Acute fatty liver of pregnancy, in which the fetus has biallelic pathogenic variants in CPT1A, has been rarely associated with CPT1A deficiency.">
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yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1527_"><span class="title" itemprop="name">Carnitine Palmitoyltransferase 1A Deficiency</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: CPT1A Deficiency, Hepatic Carnitine Palmitoyltransferase 1 Deficiency</div><p class="contribs">Lee K, Pritchard A, Ahmad A.</p><p class="fm-aai"><a href="#_NBK1527_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 37 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="cpt1a.Summary" itemprop="description"><h2 id="_cpt1a_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a disorder of long-chain fatty acid oxidation. Clinical manifestations usually occur in an individual with a concurrent febrile or gastrointestinal illness when energy demands are increased; onset of manifestations are usually rapid. The recognized presentations are: (1) out-of-range newborn screen (individual may be without features or with hepatic encephalopathy, hypoketotic hypoglycemia, and sudden onset of liver failure) and (2) later-onset manifestations (in the absence of newborn screening), including hepatic encephalopathy, hypoglycemia, absent or low levels of ketones, and elevated serum concentrations of liver transaminases, ammonia, and creatine kinase. Between episodes of hepatic encephalopathy, individuals appear developmentally and cognitively normal unless previous metabolic decompensation has resulted in neurologic damage. Acute fatty liver of pregnancy, in which the fetus has biallelic pathogenic variants in <i>CPT1A</i>, has been rarely associated with CPT1A deficiency.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of CPT1A deficiency is established in a proband with biallelic pathogenic variants in <i>CPT1A</i> identified by molecular genetic testing. Diminished carnitine palmitoyltransferase 1 (CPT1) enzyme activity on cultured skin fibroblasts when molecular genetic testing is not definitive may be an available option in some countries. Residual enzyme activity is 1%-5% in most individuals with CPT1A deficiency.</p></div><div><h4 class="inline">Management.</h4><p><i>Prevention of primary manifestations:</i> To prevent hypoglycemia, infants should eat frequently during the day, and cornstarch feedings may be considered continuously at night (typically after age one year); in older individuals fasting should not last more than 12 hours during illness, surgery, or medical procedures; adults need a high-carbohydrate, low-fat diet to provide a constant supply of carbohydrate energy and medium-chain triglycerides (MCT) to provide approximately one third of total calories. Prevention of hypoglycemia reduces the risk for related neurologic damage.</p><p><i>Targeted therapies:</i> Triheptanoin (an odd-carbon triglyceride) or MCT oil.</p><p><i>Supportive care</i>: Acute treatment includes prompt treatment of hypoglycemia with intravenous fluid containing 10% dextrose; the dextrose infusion should be maintained past the time that the blood glucose concentration has normalized to replete hepatic glycogen stores. Increase frequency of feeding and provide one third of total calories as triheptanoin or MCT oil. Liver enzymes and functional liver tests; consider plasma creatine kinase and urine myoglobin; consider brief hospitalization in those fasting longer than 12 hours. Long-term treatment includes high-carbohydrate diet low in long-chain fat and frequent feeding supplemented with triheptanoin or MCT oil. Consider orthotic liver transplantation in those with liver failure; educate parents on factors that increase risk of metabolic decompensation; consultation with physical therapy, occupational therapy, speech and language pathology, and developmental pediatrician as needed.</p><p><i>Surveillance:</i> Assess growth, feeding, and adherence to diet at each visit; plasma carnitine panel, acylcarnitine profile, essential fatty acids, vitamins A, D, and E, complete blood count, comprehensive metabolic panel, and creatine kinase at each visit or as needed; liver enzymes and liver function testing as clinically indicated; BUN, serum creatinine, and urinalysis as clinically indicated; assess for gastrointestinal side effects of triheptanoin or MCT oil at each visit; assess developmental and educational progress at each visit throughout childhood and adolescence; provide updated emergency management letter at each visit.</p><p><i>Agents/circumstances to avoid:</i> Prolonged fasting; potentially hepatotoxic agents such as valproate and salicylate; viral or bacterial infections; avoid overfeeding in individuals without acute illness.</p><p><i>Evaluation of relatives at risk:</i> Regardless of age, each sib of a proband should be evaluated for CPT1A deficiency, preferably by molecular genetic testing (if both pathogenic variants have been identified in the proband); enzyme analysis in cultured skin fibroblasts may be an option in some individuals.</p><p><i>Pregnancy management:</i> Pregnant women heterozygous for a known <i>CPT1A</i> pathogenic variant should be monitored for development of acute fatty liver of pregnancy.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>CPT1A deficiency is inherited in an autosomal recessive manner. When both parents are carriers of a <i>CPT1A</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. When one parent is a carrier and the other parent has two <i>CPT1A</i> pathogenic variants, each sib of an affected individual has at conception a 50% chance of being affected and a 50% chance of being an asymptomatic carrier. Heterozygotes (carriers) are asymptomatic, although heterozygous pregnant women may be at risk of developing acute fatty liver of pregnancy if the fetus has two pathogenic <i>CPT1A</i> alleles. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the <i>CPT1A</i> pathogenic variants in the family are known.</p></div></div><div id="cpt1a.Diagnosis"><h2 id="_cpt1a_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for carnitine palmitoyltransferase 1A (CPT1A) deficiency have been published.</p><div id="cpt1a.Suggestive_Findings"><h3>Suggestive Findings</h3><div id="cpt1a.Scenario_1_Infantile_Onset_includi"><h4>Scenario 1: Infantile Onset (including abnormal newborn screening result and symptomatic neonate)</h4><p><b>Newborn screening</b> (NBS) for CPT1A deficiency is primarily based on the elevation of free carnitine (C0) and an increased ratio of free carnitine to the sum of C16:0 (palmitoylcarnitine) plus C18 acylcarnitines (C18:1, oleic acid, and C18:2 linoleic acid) on an NBS blood spot [<a class="bibr" href="#cpt1a.REF.fingerhut.2001.1763" rid="cpt1a.REF.fingerhut.2001.1763">Fingerhut et al 2001</a>, <a class="bibr" href="#cpt1a.REF.sim.2001.51" rid="cpt1a.REF.sim.2001.51">Sim et al 2001</a>]. Some states also include low C16 levels in their NBS analysis [<a class="bibr" href="#cpt1a.REF.dowsett.2017.10" rid="cpt1a.REF.dowsett.2017.10">Dowsett et al 2017</a>] (see <a href="https://www.acmg.net/PDFLibrary/C0_C16+C18.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ACMG ACT Sheet</a>).</p><p>Cutoffs for C0 and C0:C16+C18 vary by state. If the NBS is abnormal, follow-up acylcarnitine profile and measurement of plasma-free and total carnitine is recommended. However, since acylcarnitine measurements in infants with CPT1A deficiency can normalize after the initial NBS [<a class="bibr" href="#cpt1a.REF.borch.2012.11" rid="cpt1a.REF.borch.2012.11">Borch et al 2012</a>, <a class="bibr" href="#cpt1a.REF.dowsett.2017.10" rid="cpt1a.REF.dowsett.2017.10">Dowsett et al 2017</a>, <a class="bibr" href="#cpt1a.REF.boonsimma.2021.104034" rid="cpt1a.REF.boonsimma.2021.104034">Boonsimma et al 2021</a>], molecular genetic testing is required to <a href="#cpt1a.Establishing_the_Diagnosis">establish the diagnosis</a> even in those with an abnormal NBS. Note: carnitine palmitoyltransferase 1 (CPT1) enzyme testing on skin fibroblasts may also help establish the diagnosis in situations where molecular testing is equivocal (Establishing the Diagnosis, <a href="#cpt1a.Specialized_Biochemical_Testing">Specialized Biochemical Testing</a>).</p><p>While most newborns with an out-of-range NBS are asymptomatic, the following medical interventions need to begin immediately on receipt of an abnormal NBS result while additional testing is performed to determine whether this a true positive NBS result and to establish the diagnosis of CPT1A deficiency:</p><ul><li class="half_rhythm"><div>Avoidance of prolonged fasting</div></li><li class="half_rhythm"><div>Anticipatory guidance to the family regarding signs and manifestations of concern (lethargy, poor feeding) that would warrant emergent evaluation</div></li></ul><p><b>Suggestive clinical and biochemical findings in a symptomatic infant</b> are usually triggered by fasting or intercurrent illnesses, and include hypoketotic hypoglycemia, hepatomegaly, and elevated liver transaminases. Clinical presentation in the newborn period is also possible when breast feeding is insufficiently established and caloric intake is inadequate.</p></div><div id="cpt1a.Scenario_2_Symptomatic_Individual"><h4>Scenario 2: Symptomatic Individual</h4><p>Symptomatic CPT1A deficiency is defined as an individual who has either atypical findings associated with later-onset CPT1A deficiency or untreated infantile-onset CPT1A deficiency resulting from any of the following: NBS not performed, metabolic abnormalities not sufficiently elevated to be considered "out of range" at time of NBS resulting in a false negative, or caregivers not adherent with recommended treatment following a positive NBS result.</p><p>Note: NBS may not identify all affected individuals, especially if metabolic abnormalities are in range at the time of NBS. NBS with acylcarnitine profile alone (without molecular genetic testing) often misses individuals homozygous for the <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Pro479Leu</a> pathogenic variant common in the Inuit population [<a class="bibr" href="#cpt1a.REF.gessner.2011.124" rid="cpt1a.REF.gessner.2011.124">Gessner et al 2011</a>].</p><p><b>Clinical manifestations</b> may include:</p><ul><li class="half_rhythm"><div>Lethargy, altered mental status, and/or seizures (related to hypoglycemia)</div></li><li class="half_rhythm"><div>Hepatomegaly</div></li><li class="half_rhythm"><div>Muscle weakness</div></li><li class="half_rhythm"><div>Sudden unexplained death</div></li></ul><p>
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<b>Supportive laboratory findings</b>
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</p><ul><li class="half_rhythm"><div><b>Hypoketotic hypoglycemia</b> defined as low blood glucose concentration (<40 mg/dL) in the absence of ketone bodies in the urine</div></li><li class="half_rhythm"><div><b>Elevated liver enzymes.</b> Aspartate transaminase and alanine transaminase that are two- to tenfold the upper limit of normal</div></li><li class="half_rhythm"><div><b>Hyperammonemia.</b> Plasma ammonia concentrations may be elevated.</div></li><li class="half_rhythm"><div><b>Elevated total serum carnitine</b> in the range of 70-170 µmol/L (normal total serum carnitine: 25-69 µmol/L). The elevation of total carnitine and hypoketotic hypoglycemia should increase suspicion specifically for CPT1A deficiency.</div></li><li class="half_rhythm"><div><b>Elevated ratio of C0:C16+C18 acylcarnitines.</b> CPT1A deficiency is characterized by marked reduction in the synthesis of all acylcarnitine species and increased levels of free carnitine (C0). This finding is very suggestive for this disorder.</div></li><li class="half_rhythm"><div><b>Urine organic acids</b> may demonstrate elevated dodecanedioic acid during an acute crisis and for several days following [<a class="bibr" href="#cpt1a.REF.korman.2005.337" rid="cpt1a.REF.korman.2005.337">Korman et al 2005</a>].</div></li></ul><p><b>Family history</b> is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p></div></div><div id="cpt1a.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of CPT1A deficiency <b>is established</b> in a proband with biallelic pathogenic (or likely pathogenic) variants in <i>CPT1A</i> identified by molecular genetic testing<i>.</i></p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bibr" href="#cpt1a.REF.richards.2015.405" rid="cpt1a.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (2) Identification of biallelic <i>CPT1A</i> variants of uncertain significance (or of one known <i>CPT1A</i> pathogenic variant and one <i>CPT1A</i> variant of uncertain significance) does not establish or rule out the diagnosis. (3) In instances in which the results of molecular genetic testing are unclear (e.g., identification of variants of uncertain significance or only one <i>CPT1A</i> pathogenic variant is identified), CPT1 enzyme testing on skin fibroblasts may establish the diagnosis (see Establishing the Diagnosis, <a href="#cpt1a.Specialized_Biochemical_Testing">Specialized Biochemical Testing</a>).</p><div id="cpt1a.Scenario_1_Abnormal_NBS_Result"><h4>Scenario 1: Abnormal NBS Result</h4><p>When NBS results and/or other laboratory findings suggest the diagnosis of CPT1A deficiency, molecular genetic testing approaches can include <b>single-gene testing</b> or use of a <b>multigene panel</b>.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>CPT1A</i> can be performed first to detect missense, nonsense, and splice site variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.</div><div class="half_rhythm">Note: A limited number of clinical laboratories may only offer targeted molecular testing for a single common <i>CPT1A</i> pathogenic variant found in specific populations (e.g., <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Pro479Leu</a> common in the Inuit population in the Arctic; see <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">Table 8</a>).</div></li><li class="half_rhythm"><div class="half_rhythm">A <b>fatty acid oxidation disorder</b> or other (hyperammonemia, hypoglycemia, metabolic newborn screening, metabolic myopathy, neuromuscular, rhabdomyolysis) <b>multigene panel</b> that includes <i>CPT1A</i> and other genes of interest (see <a href="#cpt1a.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul></div><div id="cpt1a.Scenario_2_Symptomatic_Individual_1"><h4>Scenario 2: Symptomatic Individual</h4><p>A symptomatic individual who has findings associated with later diagnosis of CPT1A deficiency or untreated infantile-onset CPT1A deficiency (resulting from NBS not performed or not detected during NBS) typically can be evaluated with a multigene fatty acid oxidation disorder panel or other similar panel. Single-gene testing can be performed if the plasma acylcarnitine and total serum carnitine results and ratios are strongly suggestive of CPT1A deficiency.</p><p>When the individual is critically ill or the diagnosis of CPT1A deficiency has not been specifically considered, <b>comprehensive</b>
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<b>genomic testing</b> is an option. <b>Exome sequencing</b> is most often used; <b>genome sequencing</b> is also possible. To date, most reported pathogenic variants (within HGMD) are either within exons or canonical splice site junctions and are likely to be identified on exome sequencing.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1aTmoleculargenetictestingusedi"><a href="/books/NBK1527/table/cpt1a.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobcpt1aTmoleculargenetictestingusedi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.T.molecular_genetic_testing_used_i"><a href="/books/NBK1527/table/cpt1a.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobcpt1aTmoleculargenetictestingusedi">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Carnitine Palmitoyltransferase 1A Deficiency </p></div></div></div><div id="cpt1a.Specialized_Biochemical_Testing"><h4>Specialized Biochemical Testing</h4><p><b>CPT1 enzyme activity on cultured skin fibroblasts.</b> In instances where results of molecular genetic testing are inconclusive (e.g., identification of variants of uncertain significance or only one pathogenic variant is identified), CPT1 enzyme testing on skin fibroblasts may establish the diagnosis. Residual CPT1 enzyme activity is 1%-5% in most individuals with CPT1A deficiency. The clinical availability of enzyme testing varies with time and is not currently available in the United States. The authors are aware of a single lab, the Laboratory Genetic Metabolic Diseases in Amsterdam, the Netherlands, that offers CPT1 enzyme testing on skin fibroblasts (<a href="https://www.amc.nl/web/laboratory-genetic-metabolic-diseases-lgmd.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.amc.nl</a>).</p></div></div></div><div id="cpt1a.Clinical_Characteristics"><h2 id="_cpt1a_Clinical_Characteristics_">Clinical Characteristics</h2><div id="cpt1a.Clinical_Description"><h3>Clinical Description</h3><p>The mitochondrial membrane protein encoded by <i>CPT1A</i> enables oxidation of long-chain fatty acyl-coenzyme A molecules in the liver to provide an alternative source of energy when liver glycogen reserves have been significantly reduced, most often during fasting or intercurrent illness (see <a href="#cpt1a.Molecular_Pathogenesis">Molecular Pathogenesis</a>). This pathway fuels ketogenesis for metabolism in other tissues that cannot oxidize fatty acids.</p><p>Thus, clinical manifestations of CPT1A deficiency usually occur with a febrile or gastrointestinal illness when energy demands are increased. Although the precipitating illness may be a relatively common infectious disease, onset of manifestations is usually rapid. Age of onset of manifestations can vary from the newborn period to adulthood, and some individuals are asymptomatic.</p><p>Recognition of CPT1A deficiency and initiating management to prevent lipolysis reduces the episodes of decompensation [<a class="bibr" href="#cpt1a.REF.stoler.2004.679" rid="cpt1a.REF.stoler.2004.679">Stoler et al 2004</a>, <a class="bibr" href="#cpt1a.REF.stanley.2014" rid="cpt1a.REF.stanley.2014">Stanley et al 2014</a>] (see <a href="#cpt1a.Management">Management</a>).</p><p><b>Hypoglycemia.</b> Hypoketotic hypoglycemia can present in the neonatal period or later in life. In the neonatal period, this may initially mimic the transitional hypoglycemia of the newborn (typically a decline in glucose for several hours after birth that increases with regular feedings and resolves within 48 hours). Hypoglycemia that is refractory to feedings, severe, or occurring longer than 48 hours after birth should raise suspicion for an inborn error of metabolism such as CPT1A deficiency.</p><p>After the neonatal period, hypoglycemia is more likely to be present in individuals with CPT1A deficiency who have an intercurrent illness or prolonged fasting.</p><p><b>Hepatic manifestations.</b> Many symptomatic individuals with CPT1A deficiency present with fasting-induced hepatic encephalopathy in early childhood or later in life, a potentially fatal presentation. Manifestations can include vomiting and altered mental status ranging from fatigue and lethargy to coma and/or death. Children who recover from fasting-induced hepatic encephalopathy are at increased risk for recurrent episodes of life-threatening illness.</p><p>Hepatomegaly is commonly reported. Laboratory findings include elevated liver enzymes and may include hyperammonemia.</p><p>Long-term liver damage is uncommon but has been reported [<a class="bibr" href="#cpt1a.REF.boonsimma.2021.104034" rid="cpt1a.REF.boonsimma.2021.104034">Boonsimma et al 2021</a>, <a class="bibr" href="#cpt1a.REF.smart.2024.107" rid="cpt1a.REF.smart.2024.107">Smart et al 2024</a>].</p><p><b>Neurologic manifestations.</b> Symptomatic individuals may manifest seizures (related to hypoglycemia) often associated with a precipitating illness or poor oral intake. Generalized tonic-clonic seizures, partial seizures, and status epilepticus have been reported.</p><p>Between episodes of metabolic decompensation, individuals with CPT1A deficiency typically appear developmentally and cognitively normal unless previous metabolic decompensation has resulted in neurologic damage (leading to motor and/or speech delays). <a class="bibr" href="#cpt1a.REF.balci.2023.101032" rid="cpt1a.REF.balci.2023.101032">Balci et al [2023]</a> have suggested global developmental delay or isolated speech delay may be possible without preceding metabolic decompensation (though notably more common with a preceding metabolic decompensation) in late-diagnosed individuals not detected by newborn screening (NBS). <a class="bibr" href="#cpt1a.REF.balci.2023.101032" rid="cpt1a.REF.balci.2023.101032">Balci et al [2023]</a> reported that clinical manifestations of delays improved with appropriate treatment of CPT1A deficiency.</p><p><b>Renal</b>
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<b>manifestations.</b> Some individuals with metabolic decompensation have also had renal tubular acidosis, with evidence of elevated urine pH and metabolic acidosis. The prevalence of this complication is unknown [<a class="bibr" href="#cpt1a.REF.falikborenstein.1992.24" rid="cpt1a.REF.falikborenstein.1992.24">Falik-Borenstein et al 1992</a>, <a class="bibr" href="#cpt1a.REF.bergman.1994.582" rid="cpt1a.REF.bergman.1994.582">Bergman et al 1994</a>, <a class="bibr" href="#cpt1a.REF.roomets.2012.473" rid="cpt1a.REF.roomets.2012.473">Roomets et al 2012</a>].</p><p><b>Cardiac and skeletal muscle manifestations.</b> Unlike with other long-chain fatty acid oxidation defects, cardiac or skeletal muscle involvement is not common [<a class="bibr" href="#cpt1a.REF.tein.1989.229" rid="cpt1a.REF.tein.1989.229">Tein et al 1989</a>, <a class="bibr" href="#cpt1a.REF.bonnefont.2004.495" rid="cpt1a.REF.bonnefont.2004.495">Bonnefont et al 2004</a>, <a class="bibr" href="#cpt1a.REF.stanley.2014" rid="cpt1a.REF.stanley.2014">Stanley et al 2014</a>]. However, several single case reports or small case series have reported cardiomyopathy in a few untreated individuals [<a class="bibr" href="#cpt1a.REF.balci.2023.101032" rid="cpt1a.REF.balci.2023.101032">Balci et al 2023</a>] or elevations in creatine kinase MM isoenzyme with concomitant myalgias [<a class="bibr" href="#cpt1a.REF.haworth.1992.553" rid="cpt1a.REF.haworth.1992.553">Haworth et al 1992</a>, <a class="bibr" href="#cpt1a.REF.olpin.2001.35" rid="cpt1a.REF.olpin.2001.35">Olpin et al 2001</a>, <a class="bibr" href="#cpt1a.REF.fontaine.2012.7" rid="cpt1a.REF.fontaine.2012.7">Fontaine et al 2012</a>, <a class="bibr" href="#cpt1a.REF.lee.2015.e19" rid="cpt1a.REF.lee.2015.e19">Lee et al 2015</a>, <a class="bibr" href="#cpt1a.REF.balci.2023.101032" rid="cpt1a.REF.balci.2023.101032">Balci et al 2023</a>]. With appropriate dietary intervention for CPT1A deficiency, these manifestations appear to resolve. Long-term skeletal muscle or cardiac complications are rare with adequate treatment.</p></div><div id="cpt1a.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p><i>CPT1A</i> pathogenic variant <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Pro479Leu</a>, observed in the Inuit population of the Arctic and sub-Arctic, is associated with a partial loss of CPT1 function but does not appear to cause acute hepatic failure [<a class="bibr" href="#cpt1a.REF.brown.2001.1134" rid="cpt1a.REF.brown.2001.1134">Brown et al 2001</a>]. In fact, most children homozygous for this variant never develop any manifestations of CPT1A deficiency. However, evidence suggests that infants who are homozygous for p.Pro479Leu have impaired fasting tolerance [<a class="bibr" href="#cpt1a.REF.gillingham.2011.261" rid="cpt1a.REF.gillingham.2011.261">Gillingham et al 2011</a>] and increased risk of infant mortality [<a class="bibr" href="#cpt1a.REF.gessner.2010.945" rid="cpt1a.REF.gessner.2010.945">Gessner et al 2010</a>, <a class="bibr" href="#cpt1a.REF.gessner.2016.933" rid="cpt1a.REF.gessner.2016.933">Gessner et al 2016</a>]. Many individuals with this variant may be missed by NBS with acylcarnitine profile alone, so Alaskan NBS programs incorporate sequencing for this variant (see <a href="https://health.alaska.gov/dph/wcfh/Pages/bloodspot/default.aspx" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">health.alaska.gov</a>).</p><p>In a study using whole-genome high-coverage sequence data of Arctic populations, p.Pro479Leu was identified as deleterious and associated with increased infant mortality in circum-Arctic populations [<a class="bibr" href="#cpt1a.REF.clemente.2014.584" rid="cpt1a.REF.clemente.2014.584">Clemente et al 2014</a>]. Some evidence suggests that the high prevalence of p.Pro479Leu among these populations is the result of historical heterozygote advantage based on beneficial health effects of the variant to either a high-fat diet or a cold environment [<a class="bibr" href="#cpt1a.REF.rajakumar.2009.1223" rid="cpt1a.REF.rajakumar.2009.1223">Rajakumar et al 2009</a>, <a class="bibr" href="#cpt1a.REF.lemas.2012.175" rid="cpt1a.REF.lemas.2012.175">Lemas et al 2012</a>, <a class="bibr" href="#cpt1a.REF.clemente.2014.584" rid="cpt1a.REF.clemente.2014.584">Clemente et al 2014</a>].</p><p><i>CPT1A</i> pathogenic variant <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Ser34Pro</a> has been described in the Micronesian population. Most homozygous individuals have been asymptomatic and did not require dietary treatment; one had mild acidosis during severe gastroenteritis but no hypoglycemia [<a class="bibr" href="#cpt1a.REF.bernhardt.2022.322" rid="cpt1a.REF.bernhardt.2022.322">Bernhardt et al 2022</a>]. Another individual experienced a mild increase in transaminases with a viral illness that self-resolved.</p><p><i>CPT1A</i> pathogenic variant <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Ser708Arg</a> has been reported in the Niuean population, with three reported homozygotes from two unrelated families who presented with typical clinical manifestations of <i>CPT1A</i> deficiency and CPT1 activity in fibroblasts at 4% of normal controls [<a class="bibr" href="#cpt1a.REF.bernhardt.2022.322" rid="cpt1a.REF.bernhardt.2022.322">Bernhardt et al 2022</a>].</p><p><i>CPT1A</i> pathogenic variant <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Gly710Glu</a> has been described in the Hutterite population. Homozygous individuals have typical manifestations of <i>CPT1A</i> deficiency in early childhood [<a class="bibr" href="#cpt1a.REF.prasad.2001.55" rid="cpt1a.REF.prasad.2001.55">Prasad et al 2001</a>, <a class="bibr" href="#cpt1a.REF.pripbuus.2001.46" rid="cpt1a.REF.pripbuus.2001.46">Prip-Buus et al 2001</a>].</p><p>In Finland, there are multiple individuals homozygous for the <i>CPT1A</i> pathogenic variant <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Lys455Thr</a> who have had typical manifestations of <i>CPT1A</i> deficiency [<a class="bibr" href="#cpt1a.REF.roomets.2012.473" rid="cpt1a.REF.roomets.2012.473">Roomets et al 2012</a>].</p></div><div id="cpt1a.Nomenclature"><h3>Nomenclature</h3><p>CPT1A deficiency has been previously described as nonketotic hypoglycemia, hepatic CPT deficiency, hepatic CPT1, and L-CPT1 deficiency.</p></div><div id="cpt1a.Prevalence"><h3>Prevalence</h3><p>CPT1A deficiency appears to be relatively rare in the general population. Combined results of NBS programs in Australia, Germany, and the United States show an incidence of CPT1A deficiency of 1:750,000-2,000,000 [<a class="bibr" href="#cpt1a.REF.lindner.2010.521" rid="cpt1a.REF.lindner.2010.521">Lindner et al 2010</a>]. Incidence of CPT1A deficiency in China has been estimated to be 1:102,388 based on NBS [<a class="bibr" href="#cpt1a.REF.zhang.2021.771922" rid="cpt1a.REF.zhang.2021.771922">Zhang et al 2021</a>].</p><p>The prevalence of CPT1A deficiency is higher in a few populations with known founder variants.</p><p>The prevalence of CPT1A deficiency in Alaskan infants is 1:780 live births [<a class="bibr" href="#cpt1a.REF.butler.2006" rid="cpt1a.REF.butler.2006">Butler & McLaughlin 2006</a>]. The frequency of homozygosity for the <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Pro479Leu</a> pathogenic variant is very high in the Alaska Native population (26.1% of live births) when ascertained by expanded NBS [<a class="bibr" href="#cpt1a.REF.gessner.2011.124" rid="cpt1a.REF.gessner.2011.124">Gessner et al 2011</a>] and is also prevalent in the Indigenous Arctic peoples of Canada, Greenland, and northeast Siberia [<a class="bibr" href="#cpt1a.REF.clemente.2014.584" rid="cpt1a.REF.clemente.2014.584">Clemente et al 2014</a>]. Homozygosity rates in the Nunavut are even higher, estimated at 64% [<a class="bibr" href="#cpt1a.REF.collins.2010.200" rid="cpt1a.REF.collins.2010.200">Collins et al 2010</a>].</p><p>The carrier rate for the <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Gly710Glu</a> pathogenic variant in the Hutterite population may be as high as 1:16 [<a class="bibr" href="#cpt1a.REF.prasad.2001.55" rid="cpt1a.REF.prasad.2001.55">Prasad et al 2001</a>].</p><p>The incidence of homozygosity for <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Ser34Pro</a>, a founder variant in the Micronesian population, is estimated to be 1:128,500 in New Zealand and 1:28,500 in Hawaii based on NBS [<a class="bibr" href="#cpt1a.REF.bernhardt.2022.322" rid="cpt1a.REF.bernhardt.2022.322">Bernhardt et al 2022</a>]. It is suspected the carrier rate may be higher, as NBS may not identify all individuals.</p><p>The <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Ser708Arg</a> founder variant identified in the Niuean population has an unknown carrier frequency.</p></div></div><div id="cpt1a.Genetically_Related_Allelic_Disord"><h2 id="_cpt1a_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>CPT1A</i>.</p></div><div id="cpt1a.Differential_Diagnosis"><h2 id="_cpt1a_Differential_Diagnosis_">Differential Diagnosis</h2><p>A number of other fetal fatty acid oxidation defects are associated with a similar risk to the heterozygous mother of developing acute fatty liver of pregnancy, typically in the third trimester, prompting further investigation of the newborn for a fatty acid oxidation defect.</p><p>The absence (or paucity) of ketone bodies during a period of hypoglycemia should increase suspicion for one of the disorders of fatty acid oxidation or the carnitine cycle, including carnitine palmitoyltransferase 1A (CPT1A) deficiency.</p><p>Selected genes of interest in the differential diagnosis of CPT1A deficiency are listed in <a href="/books/NBK1527/table/cpt1a.T.selected_genes_of_interest_in_th/?report=objectonly" target="object" rid-ob="figobcpt1aTselectedgenesofinterestinth">Table 2</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1aTselectedgenesofinterestinth"><a href="/books/NBK1527/table/cpt1a.T.selected_genes_of_interest_in_th/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobcpt1aTselectedgenesofinterestinth"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.T.selected_genes_of_interest_in_th"><a href="/books/NBK1527/table/cpt1a.T.selected_genes_of_interest_in_th/?report=objectonly" target="object" rid-ob="figobcpt1aTselectedgenesofinterestinth">Table 2. </a></h4><p class="float-caption no_bottom_margin">Selected Genes of Interest in the Differential Diagnosis of Carnitine Palmitoyltransferase 1A Deficiency </p></div></div></div><div id="cpt1a.Management"><h2 id="_cpt1a_Management_">Management</h2><p>No clinical practice guidelines for carnitine palmitoyltransferase 1A (CPT1A) deficiency have been published. In the absence of published consensus guidelines, the following recommendations are based on available evidence and literature on the subject.</p><p>When CPT1A deficiency is suspected during the diagnostic evaluation (for example, because of a suggestive carnitine and acylcarnitine profile; see <a href="#cpt1a.Suggestive_Findings">Suggestive Findings</a>), metabolic treatment including fasting precautions should be initiated immediately.</p><p>Development and evaluation of treatment plans, training and education of affected individuals and their families, and avoidance of side effects of dietary treatment (e.g., malnutrition, growth failure) require a multidisciplinary approach including multiple subspecialists, with oversight and expertise from a specialized metabolic center.</p><p>Guidelines and current management strategies for the treatment of CPT1A deficiency and other long-chain fatty acid oxidation disorders can be found at <a href="https://www.newbornscreening.info/cpt-1-carnitine-palmitoyl-transferase-deficiency-type-1/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.newbornscreening.info</a> and in <a class="bibr" href="#cpt1a.REF.vockley.2020.s147" rid="cpt1a.REF.vockley.2020.s147">Vockley [2020]</a> (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850137/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">full text</a>).</p><p>The British Inherited Metabolic Disease Group (BIMDG) website has a specific emergency management protocol for CPT1A deficiency (see <a href="https://bimdg.org.uk/emergency-guides/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Emergency Guides - BIMDG</a>).</p><div id="cpt1a.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with CPT1A deficiency, the evaluations summarized in <a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase1">Table 3</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1aTcarnitinepalmitoyltransferase1"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.T.carnitine_palmitoyltransferase_1"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase1">Table 3. </a></h4><p class="float-caption no_bottom_margin">Carnitine Palmitoyltransferase 1A Deficiency: Recommended Evaluations Following Initial Diagnosis </p></div></div></div><div id="cpt1a.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>There is no cure for CPT1A deficiency.</p><div id="cpt1a.Prevention_of_Primary_Manifestatio"><h4>Prevention of Primary Manifestations</h4><p><b>Avoidance of fasting</b> is a mainstay in treatment of CPT1A deficiency. To avoid excessive fasting in healthy individuals:</p><ul><li class="half_rhythm"><div class="half_rhythm">Neonates and infants require frequent feedings every two to three hours.</div></li><li class="half_rhythm"><div class="half_rhythm">In older individuals, overnight feedings, a bedtime snack, or 2 g/kg of uncooked cornstarch as a source of complex carbohydrates at bedtime to ensure sufficient glucose supply overnight have been used. Overnight feedings may not be necessary in those without an intercurrent illness or with pathogenic variants associated with milder disease (see <a href="#cpt1a.GenotypePhenotype_Correlations">Genotype-Phenotype Correlations</a>).</div></li><li class="half_rhythm"><div class="half_rhythm">A healthy diet containing no more than 20%-30% of total energy from dietary fat may be followed.</div></li><li class="half_rhythm"><div class="half_rhythm">In the absence of an intercurrent infection with fever or other stressing conditions, the following maximum fasting times are suggested:</div><ul><li class="half_rhythm"><div>Up to eight hours in infants between ages six and 12 months</div></li><li class="half_rhythm"><div>Up to ten hours during the second year of life</div></li><li class="half_rhythm"><div>Up to 12 hours after age two years</div></li></ul><div class="half_rhythm">Other recommendations include a general rule of thumb to avoid fasting for longer than four hours between birth and age four months, then add an additional hour of fasting for each month of age up to 12 months (see <a href="https://gmdi.org/Resources/Nutrition-Guidelines/MCAD" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Genetic Metabolic Dietitians International</a> for fasting recommendations in MCAD deficiency).</div></li></ul><p>To avoid excessive fasting in sick individuals:</p><ul><li class="half_rhythm"><div>In sick infants, breastfeeding may need to be replaced or alternated with metabolic formula containing medium-chain triglycerides (see <a href="#cpt1a.Supportive_Care">Supportive Care</a>) [<a class="bibr" href="#cpt1a.REF.vockley.2020.s147" rid="cpt1a.REF.vockley.2020.s147">Vockley 2020</a>].</div></li><li class="half_rhythm"><div>Increase frequency of feeds to reduce risk of metabolic crisis (see <a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_2/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase12">Table 5</a>).</div></li></ul></div><div id="cpt1a.Targeted_Therapies"><h4>Targeted Therapies</h4><p>
|
|
<i>In GeneReviews, a targeted therapy is one that addresses the specific underlying mechanism of disease causation (regardless of whether the therapy is significantly efficacious for one or more manifestation of the genetic condition); would otherwise not be considered without knowledge of the underlying genetic cause of the condition; or could lead to a cure</i>. —ED</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1aTcarnitinepalmitoyltransferase11"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_1/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase11"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.T.carnitine_palmitoyltransferase_1_1"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_1/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase11">Table 4. </a></h4><p class="float-caption no_bottom_margin">Carnitine Palmitoyltransferase 1A Deficiency: Targeted Therapies </p></div></div><p><b>Triheptanoin (C7).</b> Benefits include a decrease in the total days of hospitalization per year and a reduction in the episodes of rhabdomyolysis [<a href="https://pubmed.ncbi.nlm.nih.gov/26547562/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Roe & Brunengraber 2015</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/33446227/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Zöggeler et al 2021</a>]. Improvement in hepatomegaly and hypoglycemia was reported in those treated with C7 compared to pretreatment [<a class="bibr" href="#cpt1a.REF.roe.2015.260" rid="cpt1a.REF.roe.2015.260">Roe & Brunengraber 2015</a>, <a class="bibr" href="#cpt1a.REF.vockley.2015.53" rid="cpt1a.REF.vockley.2015.53">Vockley et al 2015</a>, <a class="bibr" href="#cpt1a.REF.gillingham.2017.831" rid="cpt1a.REF.gillingham.2017.831">Gillingham et al 2017</a>, <a class="bibr" href="#cpt1a.REF.vockley.2017.370" rid="cpt1a.REF.vockley.2017.370">Vockley et al 2017</a>, <a class="bibr" href="#cpt1a.REF.calvert.2018.1074" rid="cpt1a.REF.calvert.2018.1074">Calvert et al 2018</a>]. Adverse events in all of the clinical trials were similar for C7 and C8 (medium-chain triglycerides [MCT] oil) treatment and predominantly consisted of gastrointestinal manifestations (abdominal pain, diarrhea) [<a class="bibr" href="#cpt1a.REF.sklirou.2021.598760" rid="cpt1a.REF.sklirou.2021.598760">Sklirou et al 2021</a>, <a class="bibr" href="#cpt1a.REF.z_ggeler.2021.28" rid="cpt1a.REF.z_ggeler.2021.28">Zöggeler et al 2021</a>].</p></div><div id="cpt1a.Supportive_Care"><h4>Supportive Care</h4><p>Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_2/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase12">Table 5</a> for acute treatment and <a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_3/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase13">Table 6</a> for routine long-term treatment).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1aTcarnitinepalmitoyltransferase12"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_2/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase12"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.T.carnitine_palmitoyltransferase_1_2"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_2/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase12">Table 5. </a></h4><p class="float-caption no_bottom_margin">Carnitine Palmitoyltransferase 1A Deficiency: Acute Treatment </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1aTcarnitinepalmitoyltransferase13"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_3/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase13"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.T.carnitine_palmitoyltransferase_1_3"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_3/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase13">Table 6. </a></h4><p class="float-caption no_bottom_margin">Carnitine Palmitoyltransferase 1A Deficiency: Routine Long-Term Treatment </p></div></div></div></div><div id="cpt1a.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1aTcarnitinepalmitoyltransferase14"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_4/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase14"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.T.carnitine_palmitoyltransferase_1_4"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_4/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase14">Table 7. </a></h4><p class="float-caption no_bottom_margin">Carnitine Palmitoyltransferase 1A Deficiency: Recommended Surveillance </p></div></div></div><div id="cpt1a.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Avoid fasting, including during periods of preparation and recovery from planned surgery or sedation (see <a href="https://www.newenglandconsortium.org/cpt-i-deficiency" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CPT I Deficiency — New England Consortium of Metabolic Programs</a>). During periods of fasting, long-chain fatty acids are typically broken down into ketones and provide an important energy source for the liver and other tissues. Due to the metabolic block caused by this disorder, ketone production is limited, and fasting can trigger hypoketotic hypoglycemia.</p><p>Potentially hepatotoxic agents such as valproate and salicylate should be used with caution if there is evidence of hepatic dysfunction [<a class="bibr" href="#cpt1a.REF.ma.2022.1048728" rid="cpt1a.REF.ma.2022.1048728">Ma et al 2022</a>]. Adverse effects of pharmacologic agents have not been reported in individuals with CPT1A deficiency.</p><p>Avoid viral or bacterial infections.</p><p>Avoid overfeeding in individuals without acute illness to reduce long-term risk of obesity.</p></div><div id="cpt1a.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p><b>Prenatal testing of a fetus at risk.</b> Once the <i>CPT1A</i> pathogenic variants have been identified in an affected family member, prenatal testing of fetuses at risk may be performed via amniocentesis or chorionic villus sampling to allow for institution of treatment at birth. Note: If the fetus is found to have CPT1A deficiency (biallelic <i>CPT1A</i> pathogenic variants), it is appropriate to counsel the mother (heterozygous for a <i>CPT1A</i> pathogenic variant) regarding the risk for obstetric complications (see <a href="#cpt1a.Pregnancy_Management">Pregnancy Management</a>).</p><p><b>Newborn sibs.</b> For at-risk newborn sibs when prenatal testing was not performed, molecular genetic testing for the familial <i>CPT1A</i> pathogenic variants can be done in parallel with newborn screening.</p><p><b>Older sibs.</b> Because presentation in later childhood is possible, it is appropriate to evaluate the genetic status of each sib of a proband, regardless of age, to identify as early as possible those who have inherited biallelic <i>CPT1A</i> pathogenic variants and would benefit from initiation of preventive measures.</p><p>See <a href="#cpt1a.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing at-risk relatives for genetic counseling purposes.</p></div><div id="cpt1a.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Serious complications including hemolysis, elevated liver enzymes, and low platelets (HELPP)-like syndrome and acute fatty liver of pregnancy (AFLP) in a pregnant individual previously undiagnosed with CPT1A deficiency with an unaffected fetus have been reported. CPT1 enzyme activity was undetectable and molecular testing identified a homozygous pathogenic variant in the mother; the child was reported as unaffected [<a class="bibr" href="#cpt1a.REF.ylitalo.2005.2060" rid="cpt1a.REF.ylitalo.2005.2060">Ylitalo et al 2005</a>]. Pregnancy complications included hyperammonemia, metabolic acidosis, and features of disseminated intravascular coagulation.</p><p>Management of women with CPT1A deficiency during pregnancy should include avoidance of fasting, hypoglycemia, dehydration, and catabolic stress. Dietary management includes a low-fat, high-carbohydrate diet with use of triheptanoin or MCT oil. Use of triheptanoin has not been studied in pregnancy. Intrapartum management should include provision of adequate glucose infusion rate with intravenous fluids to prevent hypoglycemia, maintain anabolism, and prevent dehydration (IV infusion of 10% glucose at 1.5 times maintenance). Management by a team comprising a maternal-fetal medicine specialist and a medical/biochemical geneticist is highly recommended.</p><p>A pregnant mother who did not have CPT1A deficiency developed AFLP in two successive pregnancies; both children were subsequently shown to have deficient CPT1 enzyme activity; no molecular genetic testing was performed (though family was Inuit) [<a class="bibr" href="#cpt1a.REF.innes.2000.43" rid="cpt1a.REF.innes.2000.43">Innes et al 2000</a>].</p><p>Although data are limited, it is prudent to counsel heterozygous females who are carrying a fetus with biallelic <i>CPT1A</i> pathogenic variants and females homozygous for <i>CPT1A</i> pathogenic variants regarding the risk for obstetric complications. There is no known risk for obstetric complications if the mother is heterozygous for a <i>CPT1A</i> pathogenic variant and the fetus is unaffected.</p><p>Women who have had one child with CPT1A deficiency following an uneventful pregnancy remain at risk for AFLP in subsequent pregnancies with an affected fetus. In any pregnancies that follow identification of a child with CPT1A deficiency, it is recommended that liver function testing be performed at each prenatal visit during the first two trimesters and more frequently during the third trimester, when the risk for AFLP is greatest. Management by a team comprising a maternal-fetal medicine specialist and a medical/biochemical geneticist is highly recommended.</p></div><div id="cpt1a.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="cpt1a.Genetic_Counseling"><h2 id="_cpt1a_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="cpt1a.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Carnitine palmitoyltransferase 1A (CPT1A) deficiency is inherited in an autosomal recessive manner.</p></div><div id="cpt1a.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected individual are presumed to be heterozygous for a <i>CPT1A</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a <i>CPT1A</i> pathogenic variant and to allow reliable recurrence risk assessment. If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#cpt1a.REF.j_nsson.2017.519" rid="cpt1a.REF.j_nsson.2017.519">Jónsson et al 2017</a>]. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are not at risk for CPT1A deficiency. Although published data is limited, pregnant female carriers may be at risk of developing acute fatty liver of pregnancy if the fetus has CPT1A deficiency.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for a <i>CPT1A</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of inheriting neither of the familial pathogenic variants.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are not at risk for CPT1A deficiency. Pregnant female carriers may be at risk of developing acute fatty liver of pregnancy if the fetus has CPT1A deficiency.</div></li></ul><p>
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<b>Offspring of a proband</b>
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</p><ul><li class="half_rhythm"><div>Unless an affected individual's reproductive partner also has CPT1A deficiency or is a carrier, offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>CPT1A</i>.</div></li><li class="half_rhythm"><div>In populations with a high carrier rate and/or a high rate of consanguinity, it is possible that the reproductive partner of the proband may be affected or a carrier. Thus, the risk to offspring is most accurately determined after molecular genetic testing of the proband's reproductive partner.</div></li></ul><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of a <i>CPT1A</i> pathogenic variant.</p></div><div id="cpt1a.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>CPT1A</i> pathogenic variants in the family.</p></div><div id="cpt1a.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#cpt1a.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li><li class="half_rhythm"><div>Carrier testing should be considered for the reproductive partners of individuals affected with CPT1A deficiency and individuals known to be carriers of CPT1A deficiency, particularly if consanguinity is likely and/or both partners are of the same ancestral background (see <a href="#cpt1a.Prevalence">Prevalence</a>). <i>CPT1A</i> founder variants have been identified in the Hutterite, Inuit, and other populations (see <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">Table 8</a>).</div></li><li class="half_rhythm"><div>Although data are limited, it is prudent to counsel unaffected females who are heterozygous for a <i>CPT1A</i> pathogenic variant regarding the risk for obstetric complications if the fetus has CPT1A deficiency (i.e., biallelic <i>CPT1A</i> pathogenic variants; see <a href="#cpt1a.Pregnancy_Management">Pregnancy Management</a>).</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bibr" href="#cpt1a.REF.huang.2022.389" rid="cpt1a.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="cpt1a.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>CPT1A</i> pathogenic variants has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="cpt1a.Resources"><h2 id="_cpt1a_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>British Inherited Metabolic Disease Group (BIMDG)</b>
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</div><div>TEMPLE (Tools Enabling Metabolic Parents LEarning)</div><div>United Kingdom</div><div>
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<a href="https://bimdg.org.uk/store/temple//B19062_TEMPLE_CPT_1_495161_12122019.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CPT 1 DEFICIENCY</a>
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</div></li><li class="half_rhythm"><div>
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<b>MedlinePlus</b>
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</div><div>
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<a href="https://medlineplus.gov/genetics/condition/carnitine-palmitoyltransferase-i-deficiency/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Carnitine palmitoyltransferase I deficiency</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Organization for Rare Disorders (NORD)</b>
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</div><div>
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<a href="https://rarediseases.org/rare-diseases/carnitine-palmitoyltransferase-1a-deficiency/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Carnitine Palmitoyltransferase 1A Deficiency</a>
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</div></li><li class="half_rhythm"><div>
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<b>STAR-G (Screening, Technology and Research in Genetics)</b>
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</div><div>
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<a href="https://www.newbornscreening.info/cpt-1-carnitine-palmitoyl-transferase-deficiency-type-1/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CPT-1A (carnitine palmitoyl transferase deficiency-type 1)</a>
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</div></li><li class="half_rhythm"><div>
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<b>FOD Family Support Group (Fatty Oxidation Disorder)</b>
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</div><div><b>Phone:</b> 517-381-1940</div><div><b>Email:</b> deb@fodsupport.org; fodgroup@gmail.com</div><div>
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<a href="http://www.fodsupport.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">fodsupport.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Metabolic Support UK</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> 0845 241 2173</div><div>
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<a href="https://metabolicsupportuk.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">metabolicsupportuk.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Newborn Screening in Your State</b>
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</div><div>Health Resources & Services Administration</div><div>
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<a href="https://newbornscreening.hrsa.gov/your-state" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">newbornscreening.hrsa.gov/your-state</a>
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</div></li><li class="half_rhythm"><div>
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<b>United Mitochondrial Disease Foundation</b>
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</div><div><b>Phone:</b> 888-317-UMDF (8633)</div><div><b>Email:</b> info@umdf.org</div><div>
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<a href="https://www.umdf.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.umdf.org</a>
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</div></li></ul>
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</div><div id="cpt1a.Molecular_Genetics"><h2 id="_cpt1a_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1amolgenTA"><a href="/books/NBK1527/table/cpt1a.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobcpt1amolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.molgen.TA"><a href="/books/NBK1527/table/cpt1a.molgen.TA/?report=objectonly" target="object" rid-ob="figobcpt1amolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Carnitine Palmitoyltransferase 1A Deficiency: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1amolgenTB"><a href="/books/NBK1527/table/cpt1a.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobcpt1amolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.molgen.TB"><a href="/books/NBK1527/table/cpt1a.molgen.TB/?report=objectonly" target="object" rid-ob="figobcpt1amolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Carnitine Palmitoyltransferase 1A Deficiency (View All in OMIM) </p></div></div><div id="cpt1a.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Carnitine palmitoyltransferase 1A (CPT1A) deficiency is caused by a defect in the initial step of the carnitine shuttle (<a class="figpopup" href="/books/NBK1527/figure/cpt1a.F1/?report=objectonly" target="object" rid-figpopup="figcpt1aF1" rid-ob="figobcpt1aF1">Figure 1</a>). The carnitine shuttle mediates transport of long-chain fatty acyl species from the cytosol into the mitochondria for energy production by beta-oxidation. Carnitine O-palmitoyltransferase 1, liver isoform (also called carnitine palmitoyltransferase 1A; CPT1A), encoded by <i>CPT1A</i>, and located on the outer mitochondrial membrane, converts long-chain acyl-CoAs to their acylcarnitine equivalents. These are then transported into the inner mitochondrial compartment by carnitine acylcarnitine translocase and then reconverted to the acyl-CoA species by carnitine palmitoyltransferase II (CPT2) at the inner mitochondrial membrane [<a class="bibr" href="#cpt1a.REF.mcgarry.1997.1" rid="cpt1a.REF.mcgarry.1997.1">McGarry & Brown 1997</a>]. CPT1A is thus the rate-limiting factor for entry of long-chain fatty acids into the mitochondria for beta-oxidation. Mitochondrial fatty acid oxidation by the liver provides an alternative source of fuel when glycogen reserves are significantly reduced, most often due to fasting or other intercurrent illness. This pathway fuels ketogenesis for metabolism in peripheral tissues that cannot oxidize fatty acids. The reduced activity of CPT1A caused by biallelic pathogenic variants of <i>CPT1A</i> prevents fatty acids from entering the mitochondria for energy production (see <a class="figpopup" href="/books/NBK1527/figure/cpt1a.F1/?report=objectonly" target="object" rid-figpopup="figcpt1aF1" rid-ob="figobcpt1aF1">Figure 1</a>); the result is a clinical and biochemical phenotype of fasting intolerance.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figcpt1aF1" co-legend-rid="figlgndcpt1aF1"><a href="/books/NBK1527/figure/cpt1a.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figcpt1aF1" rid-ob="figobcpt1aF1"><img class="small-thumb" src="/books/NBK1527/bin/cpt1a-Image001.gif" src-large="/books/NBK1527/bin/cpt1a-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndcpt1aF1"><h4 id="cpt1a.F1"><a href="/books/NBK1527/figure/cpt1a.F1/?report=objectonly" target="object" rid-ob="figobcpt1aF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">The carnitine shuttle Acyl-coenzyme A (coA) enzymes are converted to acylcarnitines by carnitine palmitoyltransferase 1, translocated into the mitochondrial matrix by carnitine:acylcarnitine translocase, and reconverted to acyl-CoAs and free carnitine <a href="/books/NBK1527/figure/cpt1a.F1/?report=objectonly" target="object" rid-ob="figobcpt1aF1">(more...)</a></p></div></div><p>There are three isoforms of carnitine palmitoyltransferase 1 (CPT1). CPT1A is expressed in liver, kidney, lymphocytes, and skin fibroblasts. Pathogenic variants in <i>CPT1A</i> are associated with genetic disease resulting in hypoketotic hypoglycemia with fasting. Usually there is no muscle pathology involved. Since the isoform is also expressed in the kidney, renal tubular acidosis can also occur. No human disorders associated with the other isoforms of CPT1, CPT1B (encoded by <i>CPT1B</i>; skeletal muscle, heart) and CPT1C (encoded by <i>CPT1C</i>; brain) have been described [<a class="bibr" href="#cpt1a.REF.bonnefont.2004.495" rid="cpt1a.REF.bonnefont.2004.495">Bonnefont et al 2004</a>].</p><p><b>Mechanism of disease causation.</b> Loss of CPT1A function may occur from loss of mRNA expression or reduction of functional activity of CPT1A.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcpt1aTcpt1apathogenicvariantsrefere"><a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" title="Table 8. " class="img_link icnblk_img" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cpt1a.T.cpt1a_pathogenic_variants_refere"><a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">Table 8. </a></h4><p class="float-caption no_bottom_margin"><i>CPT1A</i> Pathogenic Variants Referenced in This <i>GeneReview</i> </p></div></div></div></div><div id="cpt1a.Chapter_Notes"><h2 id="_cpt1a_Chapter_Notes_">Chapter Notes</h2><div id="cpt1a.Author_Notes"><h3>Author Notes</h3><p>Note: Authors Kristen Lee and Amanda Pritchard contributed equally to this work.</p><p>Kristen Lee, MD (<a href="mailto:dev@null" data-email="ude.hcimu.dem@etsirkel" class="oemail">ude.hcimu.dem@etsirkel</a>), is a clinical and medical biochemical geneticist in the Pediatric, Adult Medical, and Cancer Genetics Clinics at Michigan Medicine. Her research interests include newborn screening, treatment of genetic disease including clinical trials for metabolic disorders, outcomes in adults with metabolic disorders, medical education for genetics trainees, and delineation of newly recognized genetic syndromes.</p><p>Amanda Pritchard, MD (<a href="mailto:dev@null" data-email="ude.hcimu.dem@enoraba" class="oemail">ude.hcimu.dem@enoraba</a>), is a clinical and medical biochemical geneticist in the Pediatric and Biochemical Genetics Clinics at Michigan Medicine. Her research and clinical interests include newborn screening, treatment and clinical trials in genetic disorders, delineation of newly recognized genetic disorders, medical education in genetics, and ophthalmic genetics.</p><p>Ayesha Ahmad, MD (<a href="mailto:dev@null" data-email="ude.hcimu.dem@haahseya" class="oemail">ude.hcimu.dem@haahseya</a>), is a clinical and clinical biochemical geneticist in the Pediatric and Biochemical Genetics Clinics at Michigan Medicine. She is actively involved in clinical research regarding biochemical genetic disorders identified by newborn screening and in several clinical trials for biochemical genetic disorders.</p><p>The authors would be happy to communicate with persons who have any questions regarding the diagnosis of CPT1A deficiency or other considerations.</p></div><div id="cpt1a.Author_History"><h3>Author History</h3><p>Ayesha Ahmad, MD (2025-present)<br />Michael J Bennett, PhD, FRCPath, DABCC; Children's Hospital of Philadelphia (2005-2025)<br />Kristen Lee, MD (2025-present)<br />Srinivas B Narayan, PhD, DABCC; Children's Hospital of Philadelphia (2005-2013)<br />Amanda Pritchard, MD (2025-present)<br />Avni B Santani, PhD, FACMG; Children's Hospital of Philadelphia (2005-2025)</p></div><div id="cpt1a.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>20 February 2025 (gf/sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>17 March 2016 (ma) Comprehensive update posted live</div></li><li class="half_rhythm"><div>7 September 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>24 September 2007 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>27 July 2005 (ca) Review posted live</div></li><li class="half_rhythm"><div>14 January 2005 (mb) Original submission</div></li></ul></div></div><div id="cpt1a.References"><h2 id="_cpt1a_References_">References</h2><div id="cpt1a.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="cpt1a.REF.balci.2023.101032">Balci
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MC, Karaca
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M, Selamioglu
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A, Korbeyli
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HK, Durmus
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A, Ak
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B, Kozanoglu
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T, Gokcay
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GF. A different perspective into clinical symptoms in CPT I deficiency.
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Mol Genet Metab Rep.
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2023;38:101032.
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[<a href="/pmc/articles/PMC7807521/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7807521</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33446227" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33446227</span></a>]</div></p></li></ul></div></div><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>*</dt><dd><div id="cpt1a.Tb.an1"><p class="no_top_margin">See <a href="#cpt1a.Author_Notes">Author Notes</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>†</dt><dd><div id="cpt1a.Tb.an2"><p class="no_top_margin">See <a href="#cpt1a.Author_Notes">Author Notes</a>.</p></div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1527_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Kristen Lee</span>, MD<sup><a href="#cpt1a.Tb.an1">*</a></sup><div class="affiliation small">Division of Pediatric Genetics, Metabolism, and Genomic Medicine<br />University of Michigan<br />Ann Arbor, Michigan<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.hcimu.dem@etsirkel" class="oemail">ude.hcimu.dem@etsirkel</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Amanda Pritchard</span>, MD<sup><a href="#cpt1a.Tb.an2">†</a></sup><div class="affiliation small">Division of Pediatric Genetics, Metabolism, and Genomic Medicine<br />University of Michigan<br />Ann Arbor, Michigan<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.hcimu.dem@enoraba" class="oemail">ude.hcimu.dem@enoraba</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Ayesha Ahmad</span>, MD<div class="affiliation small">Division of Pediatric Genetics, Metabolism, and Genomic Medicine<br />University of Michigan<br />Ann Arbor, Michigan<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.hcimu.dem@haahseya" class="oemail">ude.hcimu.dem@haahseya</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">July 27, 2005</span>; Last Update: <span itemprop="dateModified">February 20, 2025</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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Washington) are included with each copy; (ii) a link to the original material is provided
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whenever the material is published elsewhere on the Web; and (iii) reproducers,
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distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Lee K, Pritchard A, Ahmad A. Carnitine Palmitoyltransferase 1A Deficiency. 2005 Jul 27 [Updated 2025 Feb 20]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/carney/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/cpt2/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobcpt1aTmoleculargenetictestingusedi"><div id="cpt1a.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Carnitine Palmitoyltransferase 1A Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cpt1a.T.molecular_genetic_testing_used_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_cpt1a.T.molecular_genetic_testing_used_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_cpt1a.T.molecular_genetic_testing_used_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_cpt1a.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CPT1A</i>
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</td><td headers="hd_h_cpt1a.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_cpt1a.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>90% <sup>4</sup></td></tr><tr><td headers="hd_h_cpt1a.T.molecular_genetic_testing_used_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_cpt1a.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare <sup>6</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cpt1a.TF.1.1"><p class="no_margin">See <a href="/books/NBK1527/?report=reader#cpt1a.molgen.TA">Table A</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cpt1a.TF.1.2"><p class="no_margin">See <a href="#cpt1a.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="cpt1a.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="cpt1a.TF.1.4"><p class="no_margin">Sequence analysis also detects the common <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Gly710Glu</a> pathogenic variant in the Hutterite population [<a class="bibr" href="#cpt1a.REF.prasad.2001.55" rid="cpt1a.REF.prasad.2001.55">Prasad et al 2001</a>] and the <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Pro479Leu</a> pathogenic variant in the Inuit population [<a class="bibr" href="#cpt1a.REF.brown.2001.1134" rid="cpt1a.REF.brown.2001.1134">Brown et al 2001</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="cpt1a.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="cpt1a.TF.1.6"><p class="no_margin">Exon and multiexon deletions have been rarely reported [<a class="bibr" href="#cpt1a.REF.gobin.2002.179" rid="cpt1a.REF.gobin.2002.179">Gobin et al 2002</a>, <a class="bibr" href="#cpt1a.REF.yu.2021.1041" rid="cpt1a.REF.yu.2021.1041">Yu et al 2021</a>, <a class="bibr" href="#cpt1a.REF.zhang.2021.771922" rid="cpt1a.REF.zhang.2021.771922">Zhang et al 2021</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcpt1aTselectedgenesofinterestinth"><div id="cpt1a.T.selected_genes_of_interest_in_th" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Selected Genes of Interest in the Differential Diagnosis of Carnitine Palmitoyltransferase 1A Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.T.selected_genes_of_interest_in_th/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.T.selected_genes_of_interest_in_th_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ACADM</i>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mcad/?report=reader">Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency</a>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_4" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Because the CPT1A isoform is primarily expressed in liver, CPT1A deficiency is clinically more closely related to disorders of fatty acid oxidation & ketogenesis disorders w/hepatic phenotypes.</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HMGCL</i>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">HMG-CoA lyase deficiency (OMIM <a href="https://omim.org/entry/246450" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">246450</a>)</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HMGCS2</i>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">HMG-CoA synthase deficiency (OMIM <a href="https://omim.org/entry/605911" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">605911</a>)</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>350 genes <sup>1</sup></td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorders of oxidative phosphorylation (See <a href="/books/n/gene/mt-overview/?report=reader">Primary Mitochondrial Disorders Overview</a>.)</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD<br />MT<br />XL</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_4" rowspan="8" colspan="1" style="text-align:left;vertical-align:middle;">In the absence of manifestations involving muscle or heart, the acute hepatic presentation of CPT1A deficiency cannot be clinically distinguished from other defects of long-chain fatty acid oxidation & conditions that present as a Reye-like illness.</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ACADVL</i>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/vlcad/?report=reader">Very long-chain acyl-CoA dehydrogenase deficiency</a>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/arg1/?report=reader">
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<i>ARG1</i>
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</a>
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<br />
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<a href="/books/n/gene/args-aciduria/?report=reader">
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<i>ASL</i>
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</a>
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<br />
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<a href="/books/n/gene/ctlm/?report=reader">
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<i>ASS1</i>
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</a>
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<br />
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<i>CPS1</i>
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<br />
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<i>NAGS</i>
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<br />
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<a href="/books/n/gene/otc-def/?report=reader">
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<i>OTC</i>
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</a>
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<br />
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<a href="/books/n/gene/citrin/?report=reader">
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<i>SLC25A13</i>
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</a>
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<br />
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<a href="/books/n/gene/hhhs/?report=reader">
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<i>SLC25A15</i>
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</a>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/ucd-overview/?report=reader">Urea cycle disorders</a>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />XL <sup>2</sup></td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CPT2</i>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/cpt2/?report=reader">Carnitine palmitoyltransferase II deficiency</a>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HADHA</i>
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<br />
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<i>HADHB</i>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/lchad/?report=reader">Long-chain hydroxyacyl-CoA dehydrogenase deficiency / trifunctional protein deficiency</a>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple genes incl:<br /><i>G6PC1</i><br /><i>SLC37A4</i> <sup>3</sup></td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorders of gluconeogenesis incl <a href="/books/n/gene/gsd1/?report=reader">glycogen storage disease type I</a></td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple genes incl:<br /><i>MCEE</i><br /><i>MMAA</i><br /><i>MMAB</i><br /><i>MMADHC</i><br /><i>MMUT</i><br /><i>PCCA</i><br /><i>PCCB</i> <sup>4</sup></td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Organic acidurias such as <a href="/books/n/gene/mma/?report=reader">isolated methylmalonic acidemia</a> & <a href="/books/n/gene/propionic-a/?report=reader">propionic acidemia</a></td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC25A20</i>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/cact-def/?report=reader">Carnitine-acylcarnitine translocase deficiency</a>
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</td><td headers="hd_h_cpt1a.T.selected_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; CoA = coenzyme A; CPT1A = carnitine palmitoyltransferase 1A; HMG = 3-hydroxy-3-methylglutaryl; MT = mitochondrial; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cpt1a.TF.2.1"><p class="no_margin">
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<a class="bibr" href="#cpt1a.REF.mccormick.2018.714" rid="cpt1a.REF.mccormick.2018.714">McCormick et al [2018]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cpt1a.TF.2.2"><p class="no_margin">Ornithine transcarbamylase deficiency is inherited in an X-linked manner. The rest of the urea cycle disorders (deficiencies of NAGS, CPS1, ASS1, ASL, ARG1, ORNT1, and citrin) are inherited in an autosomal recessive manner.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="cpt1a.TF.2.3"><p class="no_margin">Pathogenic variants in <i>G6PC1</i> and <i>SLC37A4</i> are associated with glycogen storage disease type I.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="cpt1a.TF.2.4"><p class="no_margin">Pathogenic variants in <i>MCEE</i>, <i>MMAA</i>, <i>MMAB</i>, <i>MMADHC</i>, and <i>MMUT</i> are associated with isolated methylmalonic acidemia. Pathogenic variants in <i>PCCA</i> and <i>PCCB</i> are associated with propionic acidemia.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcpt1aTcarnitinepalmitoyltransferase1"><div id="cpt1a.T.carnitine_palmitoyltransferase_1" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Carnitine Palmitoyltransferase 1A Deficiency: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.T.carnitine_palmitoyltransferase_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Consultation w/metabolic physician / biochemical geneticist & specialist metabolic dietitian <sup>1</sup></b>
|
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Transfer to specialty center w/experience in mgmt of inherited metabolic diseases is strongly recommended.</div></li><li class="half_rhythm"><div>Consider short hospitalization at center of expertise for inherited metabolic conditions to provide caregivers w/detailed education (natural history, maintenance & emergency treatment, prognosis, & risks for acute encephalopathic crises).</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>If symptomatic, common presenting features are hypoketotic hypoglycemia (leading to lethargy/altered mental status), hepatomegaly/liver failure & seizures, usually precipitated by fasting or acute illness.</div></li><li class="half_rhythm"><div>This presentation is rare in newborns (however, when present, it usually manifests w/concurrent febrile or gastrointestinal illness & onset is rapid).</div></li></ul>
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</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Laboratory studies</b>
|
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Blood chemistries incl BUN, creatinine, glucose, electrolytes, & CK</div></li><li class="half_rhythm"><div>STAT ammonia</div></li><li class="half_rhythm"><div>Carnitine level</div></li><li class="half_rhythm"><div>Liver function tests</div></li><li class="half_rhythm"><div>Urinalysis</div></li></ul>
|
|
</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Baseline laboratory studies to monitor for hypoketotic hypoglycemia, liver function, & kidney function</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Additional specialists</b>
|
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider following referrals, if indicated:
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<ul><li class="half_rhythm"><div>Gastroenterologist (if concerns exist for hepatic function)</div></li><li class="half_rhythm"><div>Nephologist (if concerns exist for renal tubular acidosis)</div></li><li class="half_rhythm"><div>Neurologist (if concerns exist for encephalopathy & seizures)</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Additional studies as recommended</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Nutritionist / Feeding team eval</b>
|
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eval of feeding, anthropometric measures, & nutritional status</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
|
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of CPT1A deficiency to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support</b>
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<br />
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<b>& resources</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/psychologist &/or social worker</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To ensure understanding of diagnosis & assess parental/affected person's coping skills & <a href="#cpt1a.Resources">resources</a></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">BUN = blood urea nitrogen; CK = creatine kinase; CPT1A = carnitine palmitoyltransferase 1A; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cpt1a.TF.3.1"><p class="no_margin">Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcpt1aTcarnitinepalmitoyltransferase11"><div id="cpt1a.T.carnitine_palmitoyltransferase_1_1" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Carnitine Palmitoyltransferase 1A Deficiency: Targeted Therapies</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.T.carnitine_palmitoyltransferase_1_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Medication</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mechanism of Action</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dose</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Triheptanoin</b>
|
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<br />
|
|
<b>(Dojolvi<sup>®</sup>)</b>
|
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Synthetic 7-carbon triglyceride (source for acetyl-CoA & anaplerotic propionyl-CoA)</div></li><li class="half_rhythm"><div>Provides C5-ketone bodies that can cross blood-brain barrier, therefore providing substrates for the brain, & correcting secondary depletion of TCA cycle intermediates</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To provide ~30% of daily caloric intake <sup>1</sup></div></li><li class="half_rhythm"><div>Maximum dosing goal 2g/kg/day</div></li><li class="half_rhythm"><div>Actual maximum dose 15%-42% of total daily caloric intake from triheptanoin</div></li><li class="half_rhythm"><div>Remainder of diet modified to maintain appropriate caloric intake & balance</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Approved by FDA in June 2020 for treatment of children & adults w/LC-FAOD</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>MCT oil</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Composed of C6, C8, C10, & C12 MCT<br />(e.g., coconut oil, palm oil), naturally occurring fats that are not impacted by the enzymatic defects that result in LC-FAOD</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To provide 15%-18% of total calories</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Use of MCT oil OR triheptanoin is recommended <sup>2</sup></div></li><li class="half_rhythm"><div>MCT oil may be used if triheptanoin is not available or not tolerated.</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CoA = coenzyme A; FDA = Food and Drug Administration; LC-FAOD = long-chain fatty acid oxidation disorders; MCT = medium-chain triglycerides; TCA = tricarboxylic acid</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cpt1a.TF.4.1"><p class="no_margin"><a class="bibr" href="#cpt1a.REF.calvert.2018.1074" rid="cpt1a.REF.calvert.2018.1074">Calvert et al [2018]</a>, <a class="bibr" href="#cpt1a.REF.vockley.2019.169" rid="cpt1a.REF.vockley.2019.169">Vockley et al [2019]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cpt1a.TF.4.2"><p class="no_margin">The FDA recommends discontinuing MCT products prior to initiation of triheptanoin therapy. In the retrospective study by <a class="bibr" href="#cpt1a.REF.z_ggeler.2021.28" rid="cpt1a.REF.z_ggeler.2021.28">Zöggeler et al [2021]</a>, affected individuals were given parallel administration of MCT oil and triheptanoin.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcpt1aTcarnitinepalmitoyltransferase12"><div id="cpt1a.T.carnitine_palmitoyltransferase_1_2" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Carnitine Palmitoyltransferase 1A Deficiency: Acute Treatment</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.T.carnitine_palmitoyltransferase_1_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hydration & correction of biochemical abnormality</b>
|
|
</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Provide:
|
|
<ul><li class="half_rhythm"><div>Alternative energy sources, hydration, & correction of hypoketotic hypoglycemia;</div></li><li class="half_rhythm"><div>Sufficient amounts of IV fluid containing at least 10% dextrose w/age-appropriate electrolytes as quickly as possible to correct hypoglycemia & to prevent lipolysis & subsequent mobilization of fatty acids into mitochondria;</div></li><li class="half_rhythm"><div>1.5x maintenance rate to provide 8-10 mg/kg/min of glucose.</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Persons presenting w/profound hypoglycemia have little to no residual hepatic glycogen; continue glucose infusion beyond normalization of blood glucose to provide sufficient substrate for glycogen synthesis. Reintroduce oral feeds & reduce IV fluids when tolerated.</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dietary mgmt / Nutrition</b>
|
|
</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>↑ frequency of feeding during illness.</div></li><li class="half_rhythm"><div>Provide ~1/3 of total calories as triheptanoin or MCT oil during periods of illness (see <a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_1/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase11">Table 4</a>).</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Liver disease</b>
|
|
</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver enzymes (AST, ALT, ALP), & functional liver tests (incl PT & PTT)</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for liver failure, hepatic encephalopathy.</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>HyperCKemia/</b>
|
|
<br />
|
|
<b>Rhabdomyolysis</b>
|
|
</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider measuring in those w/acute illness:
|
|
<ul><li class="half_rhythm"><div>Plasma CK level</div></li><li class="half_rhythm"><div>Urine myoglobin</div></li></ul>
|
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">HyperCKemia has only rarely been reported in persons w/CPT1A deficiency.</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Prevention of metabolic decompensation</b>
|
|
</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider brief hospital admission for administration of IV dextrose-containing fluid if fasting >12 hours is required because of illness &/or surgical &/or medical procedures.</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ALT = alanine transaminase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; CK = creatine kinase; IV = intravenous; MCT = medium chain triglycerides; PT = prothrombin time; PTT= partial thromboplastin time</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcpt1aTcarnitinepalmitoyltransferase13"><div id="cpt1a.T.carnitine_palmitoyltransferase_1_3" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Carnitine Palmitoyltransferase 1A Deficiency: Routine Long-Term Treatment</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.T.carnitine_palmitoyltransferase_1_3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_1" rowspan="2" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Dietary mgmt / Correction of</b>
|
|
<br />
|
|
<b>biochemical abnormality</b>
|
|
</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">High-carbohydrate diet (70% of calories) that is low in long-chain fat (<20% of calories) <sup>1</sup></td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment is lifelong; metabolic dietitian critical to provide diet changes.</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Frequent feedings for infants/young children</div></li><li class="half_rhythm"><div>Consider awakening infant for feeding or overnight enteral feeding w/cornstarch if necessary.</div></li><li class="half_rhythm"><div>Frequent snacks between meals & before bedtime high in carbohydrates</div></li></ul>
|
|
</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cornstarch feedings provide a slow-release carbohydrate to prevent hypoglycemia during sleep.</div></li><li class="half_rhythm"><div>Cornstarch is generally only tolerated around age ≥1 yr due to pancreatic amylase activity.</div></li><li class="half_rhythm"><div>Maximum fasting intervals ↑ based on age of infant (see <a href="#cpt1a.Prevention_of_Primary_Manifestatio">Prevention of Primary Manifestations</a>).</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Triheptanoin</b>
|
|
<br />
|
|
<b>OR MCT oil</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_1/?report=objectonly" target="object" rid-ob="figobcpt1aTcarnitinepalmitoyltransferase11">Table 4</a>.</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Liver disease</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider orthotic liver transplantation.</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In those w/liver failure</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Risk of metabolic decompensation</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Educate parents about:
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<ul><li class="half_rhythm"><div>Factors that elicit a hypoketotic hypoglycemic crisis & early signs of decompensation;</div></li><li class="half_rhythm"><div>Risks of fasting;</div></li><li class="half_rhythm"><div>Risks during surgery, when both metabolic stress & fasting occur.</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Carry written info re child's disorder & appropriate treatment in emergency setting.</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/PT, OT, SLP, & developmental pediatrician</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In those w/developmental &/or educational concerns</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">MCT = medium-chain triglycerides; OT = occupational therapist; PT = physical therapist; SLP = speech-language pathologist</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cpt1a.TF.6.1"><p class="no_margin">Restriction of dietary fat intake is somewhat controversial with the mild and/or asymptomatic forms (such as that caused by <i>CPT1A</i> pathogenic variant <a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object" rid-ob="figobcpt1aTcpt1apathogenicvariantsrefere">p.Pro479Leu</a> common in the Inuit population in the Arctic). If the physician chooses to recommend a low-fat diet when the affected individual is well, supplementation with essential fatty acids is necessary.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcpt1aTcarnitinepalmitoyltransferase14"><div id="cpt1a.T.carnitine_palmitoyltransferase_1_4" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Carnitine Palmitoyltransferase 1A Deficiency: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.T.carnitine_palmitoyltransferase_1_4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.T.carnitine_palmitoyltransferase_1_4_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Growth/Nutrition/Feeding</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Measure length, weight, & head circumference.</div></li><li class="half_rhythm"><div>Assess feeding skills in infants/toddlers.</div></li><li class="half_rhythm"><div>Assess adherence to dietary recommendations.</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Biochemical laboratory parameters</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Plasma carnitine panel (total, free, esters)</div></li><li class="half_rhythm"><div>Plasma acylcarnitine profile</div></li><li class="half_rhythm"><div>RBC or plasma essential fatty acids</div></li><li class="half_rhythm"><div>Vitamins A, D, & E concentrations <sup>1</sup></div></li><li class="half_rhythm"><div>CBC, comprehensive metabolic panel, CK</div></li></ul>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>At each visit dependent on diet mgmt recommendations</div></li><li class="half_rhythm"><div>As clinically indicated; may be dependent on frequency of clinic visits & age (e.g., more frequent assessments when younger)</div></li></ul>
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</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hepatology</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver enzymes (AST, ALT, ALP), functional liver tests (incl PT & PTT)</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated to assess for liver failure</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Nephrology</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">BUN, serum creatinine concentration, & urinalysis for urine protein</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated to assess for renal tubular acidosis</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for gastrointestinal side effects of triheptanoin or MCT oil (e.g., diarrhea)</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit based on treatment & as clinically indicated</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess developmental & educational progress w/referrals for social services, physical therapy, occupational therapy, & speech & language services as needed</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit throughout childhood & adolescence</td></tr><tr><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Emergency management letter</b>
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</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Provide letter to affected persons (or their parents/guardians) & involved health care providers to alert them to potentially life-threatening metabolic crises & explain appropriate emergency medical treatment.</td><td headers="hd_h_cpt1a.T.carnitine_palmitoyltransferase_1_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Update at each clinic visit</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ALP = alkaline phosphatase; ALT = alanine transaminase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; CK = creatine kinase; MCT = medium-chain triglycerides; OFC = occipital frontal circumference; PT = prothrombin time; PTT = partial thromboplastin time; RBC = red blood cells</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cpt1a.TF.7.1"><p class="no_margin">Based on level/degree of fat restriction</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcpt1amolgenTA"><div id="cpt1a.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Carnitine Palmitoyltransferase 1A Deficiency: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_cpt1a.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_cpt1a.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_cpt1a.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_cpt1a.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_cpt1a.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_cpt1a.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_cpt1a.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/1374" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>CPT1A</i>
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</a>
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</td><td headers="hd_b_cpt1a.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1374" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">11q13<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_b_cpt1a.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/P50416" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Carnitine O-palmitoyltransferase 1, liver isoform</a>
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</td><td headers="hd_b_cpt1a.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://databases.lovd.nl/shared/genes/CPT1A" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CPT1A database</a>
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</td><td headers="hd_b_cpt1a.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CPT1A" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CPT1A</a>
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</td><td headers="hd_b_cpt1a.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CPT1A[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CPT1A</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="cpt1a.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcpt1amolgenTB"><div id="cpt1a.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Carnitine Palmitoyltransferase 1A Deficiency (<a href="/omim/255120,600528" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/255120" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">255120</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CARNITINE PALMITOYLTRANSFERASE I DEFICIENCY</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/600528" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">600528</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CARNITINE PALMITOYLTRANSFERASE I, LIVER; CPT1A</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobcpt1aTcpt1apathogenicvariantsrefere"><div id="cpt1a.T.cpt1a_pathogenic_variants_refere" class="table"><h3><span class="label">Table 8. </span></h3><div class="caption"><p><i>CPT1A</i> Pathogenic Variants Referenced in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1527/table/cpt1a.T.cpt1a_pathogenic_variants_refere/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cpt1a.T.cpt1a_pathogenic_variants_refere_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_1" rowspan="5" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001876.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001876<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001867.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001867<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.100T>C</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser34Pro</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant common in Micronesian population [<a class="bibr" href="#cpt1a.REF.bernhardt.2022.322" rid="cpt1a.REF.bernhardt.2022.322">Bernhardt et al 2022</a>]</td></tr><tr><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1436C>T</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro479Leu</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant common in Inuit population in Arctic [<a class="bibr" href="#cpt1a.REF.clemente.2014.584" rid="cpt1a.REF.clemente.2014.584">Clemente et al 2014</a>]</td></tr><tr><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.2122A>C</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser708Arg</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant reported in Niuean population [<a class="bibr" href="#cpt1a.REF.bernhardt.2022.322" rid="cpt1a.REF.bernhardt.2022.322">Bernhardt et al 2022</a>]</td></tr><tr><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.2129G>A</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly710Glu</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant common in Hutterite population [<a class="bibr" href="#cpt1a.REF.prasad.2001.55" rid="cpt1a.REF.prasad.2001.55">Prasad et al 2001</a>]</td></tr><tr><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1364A>C</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Lys455Thr</td><td headers="hd_h_cpt1a.T.cpt1a_pathogenic_variants_refere_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant reported in Finnish population [<a class="bibr" href="#cpt1a.REF.roomets.2012.473" rid="cpt1a.REF.roomets.2012.473">Roomets et al 2012</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobcpt1aF1"><div id="cpt1a.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1527/bin/cpt1a-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>The carnitine shuttle</p><p>Acyl-coenzyme A (coA) enzymes are converted to acylcarnitines by carnitine palmitoyltransferase 1, translocated into the mitochondrial matrix by carnitine:acylcarnitine translocase, and reconverted to acyl-CoAs and free carnitine by carnitine palmitoyltransferase 2.</p></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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