KEGG DISEASE: Phenylketonuria

KEGG

DISEASE: Phenylketonuria

Entry

H00167                      Disease

Name

Phenylketonuria;
Hyperphenylalaninemia

Subgroup

Hyperphenylalaninemia, BH4-deficient (HPABH4)
Mild non-BH4-deficient hyperphenylalaninemia (HPANBH4)

Description

Phenylketonuria (PKU) is one of the most common inborn errors of metabolism marked by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH), leading to a toxic accumulation of phenylalanine in the blood and multiple tissues and potentially to intellectual disability, delayed speech, seizures, and behavior abnormalities. Deficiency of tetrahydrobiopterin (BH4), the cofactor of PAH, is caused by defects of the enzymes in pterin biosynthesis. Because BH4 is also a cofactor of tyrosine hydroxylase and tryptophan hydroxylase in neurotransmitter synthesis, BH4-deficient hyperphenylalaninemia is characterized by neurotransmitter deficiencies.

Category

Inherited metabolic disorder

Brite

Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
  Metabolic disorders
   Inborn errors of metabolism
    5C50  Inborn errors of amino acid or other organic acid metabolism
     H00167  Phenylketonuria
Pathway-based classification of diseases [BR:br08402]
Amino acid metabolism
  nt06016  Phenylalanine and tyrosine metabolism
   H00167  Phenylketonuria

Pathway

Folate biosynthesis

Phenylalanine, tyrosine and tryptophan biosynthesis

Network

nt06016 Phenylalanine and tyrosine metabolism

Gene

(PKU) PAH [HSA:5053] [KO:K00500]
(HPABH4A) PTS [HSA:5805] [KO:K01737]
(HPABH4B) GCH1 [HSA:2643] [KO:K01495]
(HPABH4C) QDPR [HSA:5860] [KO:K00357]
(HPABH4D) PCBD1 [HSA:5092] [KO:K01724]
(HPANBH4) DNAJC12 [HSA:56521] [KO:K09532]

Drug

Pegvaliase [DR:D11077]
Sapropterin dihydrochloride [DR:D01798]

Other DBs

ICD-11:

MeSH:

OMIM:

261600 261640 233910 261630 264070 617384

Reference

Authors

Lindegren ML, Krishnaswami S, Reimschisel T, Fonnesbeck C, Sathe NA, McPheeters ML

Title

A Systematic Review of BH4 (Sapropterin) for the Adjuvant Treatment of Phenylketonuria.

Journal

JIMD Rep 8:109-19 (2013)
DOI:10.1007/8904_2012_168

Reference

PMID:18538294 (PKU)

Authors

Gersting SW, Kemter KF, Staudigl M, Messing DD, Danecka MK, Lagler FB, Sommerhoff CP, Roscher AA, Muntau AC

Title

Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability.

Journal

Am J Hum Genet 83:5-17 (2008)
DOI:10.1016/j.ajhg.2008.05.013

Reference

PMID:8178819 (HPABH4A)

Authors

Thony B, Leimbacher W, Blau N, Harvie A, Heizmann CW

Title

Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase.

Journal

Am J Hum Genet 54:782-92 (1994)

Reference

PMID:7869202 (HPABH4B)

Authors

Blau N, Ichinose H, Nagatsu T, Heizmann CW, Zacchello F, Burlina AB

Title

A missense mutation in a patient with guanosine triphosphate cyclohydrolase I deficiency missed in the newborn screening program.

Journal

J Pediatr 126:401-5 (1995)
DOI:10.1016/s0022-3476(95)70458-2

Reference

PMID:2116088 (HPABH4C)

Authors

Howells DW, Forrest SM, Dahl HH, Cotton RG

Title

Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency.

Journal

Am J Hum Genet 47:279-85 (1990)

Reference

PMID:8352282 (HPABH4D)

Authors

Citron BA, Kaufman S, Milstien S, Naylor EW, Greene CL, Davis MD

Title

Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism.

Journal

Am J Hum Genet 53:768-74 (1993)

Reference

PMID:28132689 (HPANBH4)

Authors

Anikster Y, Haack TB, Vilboux T, Pode-Shakked B, Thony B, Shen N, Guarani V, Meissner T, Mayatepek E, Trefz FK, Marek-Yagel D, Martinez A, Huttlin EL, Paulo JA, Berutti R, Benoist JF, Imbard A, Dorboz I, Heimer G, Landau Y, Ziv-Strasser L, Malicdan MCV, Gemperle-Britschgi C, Cremer K, Engels H, Meili D, Keller I, Bruggmann R, Strom TM, Meitinger T, Mullikin JC, Schwartz G, Ben-Zeev B, Gahl WA, Harper JW, Blau N, Hoffmann GF, Prokisch H, Opladen T, Schiff M

Title

Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability.

Journal

Am J Hum Genet 100:257-266 (2017)
DOI:10.1016/j.ajhg.2017.01.002

LinkDB

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