U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Mild phenylketonuria

MedGen UID:
1842357
•Concept ID:
C5680203
•
Disease or Syndrome
Synonyms: mild phenylketonuria; Mild PKU; mild PKU; mPKU; Variant phenylketonuria; variant phenylketonuria; Variant PKU; variant PKU
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0019258
Orphanet: ORPHA79253

Definition

A mild to moderate form of phenylketouria (PKU), an inborn error of amino acid metabolism, characterized by blood phenylalanine concentrations of 600-1,200 micromol/L and manifests with reduced cognitive function and behavioral and developmental disorders. Dietary phenylalanine tolerance is 400-600 mg/day. [from ORDO]

Professional guidelines

PubMed

The relationship between serum phenylalanine levels, genotype, and developmental assessment test results in non-phenylketonuria mild hyperphenylalaninemia patients.
İlgüy M, Yıldırım GK, Eyüboğlu D, Çarman KB, Yarar C
Eur J Pediatr 2024 Dec 22;184(1):99. doi: 10.1007/s00431-024-05929-1. PMID: 39710741
Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.
Jeannesson-Thivisol E, Feillet F, Chéry C, Perrin P, Battaglia-Hsu SF, Herbeth B, Cano A, Barth M, Fouilhoux A, Mention K, Labarthe F, Arnoux JB, Maillot F, Lenaerts C, Dumesnil C, Wagner K, Terral D, Broué P, de Parscau L, Gay C, Kuster A, Bédu A, Besson G, Lamireau D, Odent S, Masurel A, Guéant JL, Namour F
Orphanet J Rare Dis 2015 Dec 15;10:158. doi: 10.1186/s13023-015-0375-x. PMID: 26666653Free PMC Article
Long-term treatment of patients with mild and classical phenylketonuria by tetrahydrobiopterin.
Trefz FK, Scheible D, Frauendienst-Egger G, Korall H, Blau N
Mol Genet Metab 2005 Dec;86 Suppl 1:S75-80. Epub 2005 Oct 20 doi: 10.1016/j.ymgme.2005.06.026. PMID: 16242984

Recent clinical studies

Etiology

Evaluation of patients with phenylalanine metabolism disorder: a single center experience.
Erdol S, Bilgin H
J Pediatr Endocrinol Metab 2022 Apr 26;35(4):463-467. Epub 2022 Jan 27 doi: 10.1515/jpem-2021-0737. PMID: 35084144
Phenylalanine hydroxylase deficiency in the Slovak population: genotype-phenotype correlations and genotype-based predictions of BH4-responsiveness.
Polak E, Ficek A, Radvanszky J, Soltysova A, Urge O, Cmelova E, Kantarska D, Kadasi L
Gene 2013 Sep 10;526(2):347-55. Epub 2013 Jun 10 doi: 10.1016/j.gene.2013.05.057. PMID: 23764561
Phenylalanine hydroxylase deficiency.
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948
Tetrahydrobiopterin responsiveness: results of the BH4 loading test in 31 Spanish PKU patients and correlation with their genotype.
Desviat LR, Pérez B, Bèlanger-Quintana A, Castro M, Aguado C, Sánchez A, García MJ, Martínez-Pardo M, Ugarte M
Mol Genet Metab 2004 Sep-Oct;83(1-2):157-62. doi: 10.1016/j.ymgme.2004.06.007. PMID: 15464430
Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria.
Muntau AC, Röschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA
N Engl J Med 2002 Dec 26;347(26):2122-32. doi: 10.1056/NEJMoa021654. PMID: 12501224

Diagnosis

Phenylalanine hydroxylase deficiency in the Slovak population: genotype-phenotype correlations and genotype-based predictions of BH4-responsiveness.
Polak E, Ficek A, Radvanszky J, Soltysova A, Urge O, Cmelova E, Kantarska D, Kadasi L
Gene 2013 Sep 10;526(2):347-55. Epub 2013 Jun 10 doi: 10.1016/j.gene.2013.05.057. PMID: 23764561
Phenylalanine hydroxylase deficiency.
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948
The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.
Blau N, Erlandsen H
Mol Genet Metab 2004 Jun;82(2):101-11. doi: 10.1016/j.ymgme.2004.03.006. PMID: 15171997
Tetrahydrobiopterin sensitivity in German patients with mild phenylalanine hydroxylase deficiency.
Lindner M, Steinfeld R, Burgard P, Schulze A, Mayatepek E, Zschocke J
Hum Mutat 2003 Apr;21(4):400. doi: 10.1002/humu.9117. PMID: 12655554
Results of screening for phenylalanine and other amino acid disturbances among pregnant women.
Hyánek J, Homolka J, Trnka J, Seemanová E, Cervenka J, Tresohlavá Z, Kapras J, Dolezal A, Srácek J, Vácha V, Hoza J, Losan F, Nevsímalová S, Malá M, Viletová H
J Inherit Metab Dis 1980;2(3):59-63. doi: 10.1007/BF01801720. PMID: 6796761

Therapy

Phenylalanine hydroxylase deficiency in the Slovak population: genotype-phenotype correlations and genotype-based predictions of BH4-responsiveness.
Polak E, Ficek A, Radvanszky J, Soltysova A, Urge O, Cmelova E, Kantarska D, Kadasi L
Gene 2013 Sep 10;526(2):347-55. Epub 2013 Jun 10 doi: 10.1016/j.gene.2013.05.057. PMID: 23764561
Phenylalanine hydroxylase deficiency.
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948
The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.
Blau N, Erlandsen H
Mol Genet Metab 2004 Jun;82(2):101-11. doi: 10.1016/j.ymgme.2004.03.006. PMID: 15171997
Tetrahydrobiopterin sensitivity in German patients with mild phenylalanine hydroxylase deficiency.
Lindner M, Steinfeld R, Burgard P, Schulze A, Mayatepek E, Zschocke J
Hum Mutat 2003 Apr;21(4):400. doi: 10.1002/humu.9117. PMID: 12655554
Treatable neurotransmitter deficiency in mild phenylketonuria.
Bonafé L, Blau N, Burlina AP, Romstad A, Güttler F, Burlina AB
Neurology 2001 Sep 11;57(5):908-11. doi: 10.1212/wnl.57.5.908. PMID: 11552030

Prognosis

Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.
Jeannesson-Thivisol E, Feillet F, Chéry C, Perrin P, Battaglia-Hsu SF, Herbeth B, Cano A, Barth M, Fouilhoux A, Mention K, Labarthe F, Arnoux JB, Maillot F, Lenaerts C, Dumesnil C, Wagner K, Terral D, Broué P, de Parscau L, Gay C, Kuster A, Bédu A, Besson G, Lamireau D, Odent S, Masurel A, Guéant JL, Namour F
Orphanet J Rare Dis 2015 Dec 15;10:158. doi: 10.1186/s13023-015-0375-x. PMID: 26666653Free PMC Article
Phenylalanine hydroxylase deficiency in the Slovak population: genotype-phenotype correlations and genotype-based predictions of BH4-responsiveness.
Polak E, Ficek A, Radvanszky J, Soltysova A, Urge O, Cmelova E, Kantarska D, Kadasi L
Gene 2013 Sep 10;526(2):347-55. Epub 2013 Jun 10 doi: 10.1016/j.gene.2013.05.057. PMID: 23764561
Assessment of tetrahydrobiopterin responsiveness in Turkish hyperphenylalaninemic patients.
Yildirim S, Tokatli A, Yilmaz E, Coşkun T
Turk J Pediatr 2007 Jan-Mar;49(1):1-6. PMID: 17479638
Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria.
Muntau AC, Röschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA
N Engl J Med 2002 Dec 26;347(26):2122-32. doi: 10.1056/NEJMoa021654. PMID: 12501224
The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations.
Konecki DS, Lichter-Konecki U
Hum Genet 1991 Aug;87(4):377-88. doi: 10.1007/BF00197152. PMID: 1679029

Clinical prediction guides

Phenylalanine hydroxylase deficiency in the Slovak population: genotype-phenotype correlations and genotype-based predictions of BH4-responsiveness.
Polak E, Ficek A, Radvanszky J, Soltysova A, Urge O, Cmelova E, Kantarska D, Kadasi L
Gene 2013 Sep 10;526(2):347-55. Epub 2013 Jun 10 doi: 10.1016/j.gene.2013.05.057. PMID: 23764561
Mechanisms underlying responsiveness to tetrahydrobiopterin in mild phenylketonuria mutations.
Pey AL, Pérez B, Desviat LR, Martínez MA, Aguado C, Erlandsen H, Gámez A, Stevens RC, Thórólfsson M, Ugarte M, Martínez A
Hum Mutat 2004 Nov;24(5):388-99. doi: 10.1002/humu.20097. PMID: 15459954
Tetrahydrobiopterin sensitivity in German patients with mild phenylalanine hydroxylase deficiency.
Lindner M, Steinfeld R, Burgard P, Schulze A, Mayatepek E, Zschocke J
Hum Mutat 2003 Apr;21(4):400. doi: 10.1002/humu.9117. PMID: 12655554
Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria.
Muntau AC, Röschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA
N Engl J Med 2002 Dec 26;347(26):2122-32. doi: 10.1056/NEJMoa021654. PMID: 12501224
The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations.
Konecki DS, Lichter-Konecki U
Hum Genet 1991 Aug;87(4):377-88. doi: 10.1007/BF00197152. PMID: 1679029

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Reviews

    Related information

    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...