KEGG   DISEASE: Phenylketonuria
H00167                      Disease                                
Hyperphenylalaninemia, BH4-deficient (HPABH4)
Mild non-BH4-deficient hyperphenylalaninemia (HPANBH4)
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.
Inherited metabolic disorder
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
hsa00790  Folate biosynthesis
hsa00400  Phenylalanine, tyrosine and tryptophan biosynthesis
nt06016 Phenylalanine and tyrosine metabolism
(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]
Pegvaliase [DR:D11077]
Sapropterin dihydrochloride [DR:D01798]
Other DBs
ICD-11: 5C50.0
ICD-10: E70.0
MeSH: D010661
OMIM: 261600 261640 233910 261630 264070 617384
Lindegren ML, Krishnaswami S, Reimschisel T, Fonnesbeck C, Sathe NA, McPheeters ML
A Systematic Review of BH4 (Sapropterin) for the Adjuvant Treatment of Phenylketonuria.
JIMD Rep 8:109-19 (2013)
PMID:18538294 (PKU)
Gersting SW, Kemter KF, Staudigl M, Messing DD, Danecka MK, Lagler FB, Sommerhoff CP, Roscher AA, Muntau AC
Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability.
Am J Hum Genet 83:5-17 (2008)
PMID:8178819 (HPABH4A)
Thony B, Leimbacher W, Blau N, Harvie A, Heizmann CW
Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase.
Am J Hum Genet 54:782-92 (1994)
PMID:7869202 (HPABH4B)
Blau N, Ichinose H, Nagatsu T, Heizmann CW, Zacchello F, Burlina AB
A missense mutation in a patient with guanosine triphosphate cyclohydrolase I deficiency missed in the newborn screening program.
J Pediatr 126:401-5 (1995)
PMID:2116088 (HPABH4C)
Howells DW, Forrest SM, Dahl HH, Cotton RG
Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency.
Am J Hum Genet 47:279-85 (1990)
PMID:8352282 (HPABH4D)
Citron BA, Kaufman S, Milstien S, Naylor EW, Greene CL, Davis MD
Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism.
Am J Hum Genet 53:768-74 (1993)
PMID:28132689 (HPANBH4)
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
Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability.
Am J Hum Genet 100:257-266 (2017)

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