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Disorders of tetrahydrobiopterin metabolism and their treatment.
Curr Drug Metab. 2002 Apr; 3(2):123-31.CD

Abstract

Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine metabolism in liver and neurotransmitters biosynthesis in brain. BH4 is the essential cofactor in the enzymatic hydroxylation of 3 aromatic amino acids (phenylalanine, tyrosine, and tryptophan). BH4 is synthesized from guanosine triphosphate (GTP) catalyzed by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase, and sepiapterin reductase (SPR), and in aromatic amino acids hydoxylating system is regenerated by pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR). To date, 4 enzyme deficiencies (GTPCH, PTPS, DHPR, PCD) have been reported and they all follow an autosomal recessive mode of inheritance. The incidence of BH4 deficiency is at 1 in 1,000,000, except that in Taiwanese (much higher than in Japanese and Caucasians). BH4 deficiency has been diagnosed in patients with hyperphenylalaninemia (HPA) by neonatal mass-screening based on BH4 oral loading tests, analysis of urinary or serum pteridines, and measurement of dihydropterindine reductase (DHPR) activity in blood from a Guthrie card. BH4 deficiency without treatment causes combined symptoms of HPA and neurotransmitter (dopamine, norepinephrine, epinephrine, and serotonin) deficiency, such as red hair, psychomotor retardation, and progressive neurological deterioration. Treatment of BH4 deficiencies consists of BH4 supplementation (2-20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precausers (L-dopa/CarbiDOPA and 5-hydroxytryptophan), and supplements of folinic acid in DHPR deficiency.

Authors+Show Affiliations

Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan. shintakuh@med.osaka-cu.ac.jp

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

12003346

Citation

Shintaku, H. "Disorders of Tetrahydrobiopterin Metabolism and Their Treatment." Current Drug Metabolism, vol. 3, no. 2, 2002, pp. 123-31.
Shintaku H. Disorders of tetrahydrobiopterin metabolism and their treatment. Curr Drug Metab. 2002;3(2):123-31.
Shintaku, H. (2002). Disorders of tetrahydrobiopterin metabolism and their treatment. Current Drug Metabolism, 3(2), 123-31.
Shintaku H. Disorders of Tetrahydrobiopterin Metabolism and Their Treatment. Curr Drug Metab. 2002;3(2):123-31. PubMed PMID: 12003346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disorders of tetrahydrobiopterin metabolism and their treatment. A1 - Shintaku,H, PY - 2002/5/11/pubmed PY - 2002/10/17/medline PY - 2002/5/11/entrez SP - 123 EP - 31 JF - Current drug metabolism JO - Curr Drug Metab VL - 3 IS - 2 N2 - Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine metabolism in liver and neurotransmitters biosynthesis in brain. BH4 is the essential cofactor in the enzymatic hydroxylation of 3 aromatic amino acids (phenylalanine, tyrosine, and tryptophan). BH4 is synthesized from guanosine triphosphate (GTP) catalyzed by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase, and sepiapterin reductase (SPR), and in aromatic amino acids hydoxylating system is regenerated by pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR). To date, 4 enzyme deficiencies (GTPCH, PTPS, DHPR, PCD) have been reported and they all follow an autosomal recessive mode of inheritance. The incidence of BH4 deficiency is at 1 in 1,000,000, except that in Taiwanese (much higher than in Japanese and Caucasians). BH4 deficiency has been diagnosed in patients with hyperphenylalaninemia (HPA) by neonatal mass-screening based on BH4 oral loading tests, analysis of urinary or serum pteridines, and measurement of dihydropterindine reductase (DHPR) activity in blood from a Guthrie card. BH4 deficiency without treatment causes combined symptoms of HPA and neurotransmitter (dopamine, norepinephrine, epinephrine, and serotonin) deficiency, such as red hair, psychomotor retardation, and progressive neurological deterioration. Treatment of BH4 deficiencies consists of BH4 supplementation (2-20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precausers (L-dopa/CarbiDOPA and 5-hydroxytryptophan), and supplements of folinic acid in DHPR deficiency. SN - 1389-2002 UR - https://wwww.unboundmedicine.com/medline/citation/12003346/Disorders_of_tetrahydrobiopterin_metabolism_and_their_treatment_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1389-2002&volume=3&issue=2&spage=123&aulast=Shintaku DB - PRIME DP - Unbound Medicine ER -
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