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Review
. 2018 Dec;6(24):472.
doi: 10.21037/atm.2018.12.39.

Organic acid disorders

Jessica Ramsay  1 , Jacob Morton  1 , Marie Norris  2 , Shibani Kanungo  1
Affiliations
Review

Organic acid disorders

Jessica Ramsay et al. Ann Transl Med. 2018 Dec.

Abstract

Organic acids (OAs) are intermediary products of several amino acid catabolism or degradation via multiple biochemical pathways for energy production. Vitamins or co-factors are often quintessential elements in such degradation pathways and OA metabolism. OAs that result from enzyme defects in these pathways can be identified in body fluids utilizing gas chromatography-mass spectrometry techniques (GC/MS). OAs are silent contributor to acid base imbalance and can affect nitrogen balance and recycling. Since OA production occurs in distal steps of a specific amino acid catabolism, offending amino acid accumulation is not characteristic. OA disorders as inborn errors of metabolism (IEM) are included in differential diagnosis of metabolic acidosis, as the common mnemonic MUDPILES taught in medical schools. High anion gap metabolic acidosis with hyperammonemia is a characteristic OA biochemical finding. VOMIT (valine, odd chain fatty acids, methionine, isoleucine, and threonine) is a smart acronym and a common clinical presentation of OA disorders and can present as early life-threatening illness, prior to Newborn Screening results availability. Easy identification and available medical formula make the field of metabolic nutrition vital for management of OA disorders. Treatment strategies also involve cofactor/vitamin utilization to aid specific pathways and disorder management. Optimal metabolic control and regular monitoring is key to long-term management and prevention of morbidity, disability and mortality. Prompt utilization of acute illness protocol (AIP) or emergency protocol and disorder specific education of family members or caregivers, primary care physicians and local emergency health care facilities; cautiously addressing common childhood illnesses in patients with OA disorders, can help avoid poor short- and long-term morbidity, disability and mortality outcomes.

Keywords: Organic acids (OAs); high anion gap metabolic acidosis; hyperammonemia; neutropenia; valine, odd chain fatty acids, methionine, isoleucine, and threonine (VOMIT).

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Overview of organic acid (OA) metabolism. Enzyme names are represented in italics and corresponding intra-mitochondrial enzyme deficiencies are shown in the red star shapes. Green line represents mitochondrial membrane. MSUD, maple syrup urine disease; IBDD, isobutyryl-CoA dehydrogenase deficiency; HIBCHD, β-hydroxybutyryl-CoA dehydrogenase deficiency; MMSDHD, methylmalonate semialdehyde dehydrogenase deficiency; DLDD, Dihydrolipoamide dehydrogenase deficiency; MCCD, β-methylcrotonyl-CoA carboxylase deficiency; MGCA, β-methylglutaconic aciduria; HMGCLD, HMG-CoA lyase deficiency; GCDH, glutaryl-CoA dehydrogenase deficiency.
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