9dtw

Structural highlights

Disease

DHPR_HUMAN Defects in QDPR are the cause of BH4-deficient hyperphenylalaninemia type C (HPABH4C) [MIM:261630; also called dihydropteridine reductase deficiency (DHPR deficiency) or hyperphenylalaninemia tetrahydrobiopterin-deficient due to DHPR deficiency or quinoid dihydropteridine reductase deficiency (QDPR deficiency). HPABH4C is a rare autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. These patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated.^{[1] [2] [3] [4] [5]}

Function

DHPR_HUMAN The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases.

References

1. ↑ Dianzani I, de Sanctis L, Smooker PM, Gough TJ, Alliaudi C, Brusco A, Spada M, Blau N, Dobos M, Zhang HP, Yang N, Ponzone A, Armarego WL, Cotton RG. Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations. Hum Mutat. 1998;12(4):267-73. PMID:9744478 doi:<267::AID-HUMU8>3.0.CO;2-C 10.1002/(SICI)1098-1004(1998)12:4<267::AID-HUMU8>3.0.CO;2-C
2. ↑ Dianzani I, Howells DW, Ponzone A, Saleeba JA, Smooker PM, Cotton RG. Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency. J Med Genet. 1993 Jun;30(6):465-9. PMID:8326489
3. ↑ 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. 1990 Aug;47(2):279-85. PMID:2116088
4. ↑ Smooker PM, Gough TJ, Cotton RG, Alliaudi C, de Sanctis L, Dianzani I. A series of mutations in the dihydropteridine reductase gene resulting in either abnormal RNA splicing or DHPR protein defects. Mutations in brief no. 244. Online. Hum Mutat. 1999;13(6):503-4. PMID:10408783 doi:<503::AID-HUMU13>3.0.CO;2-F 10.1002/(SICI)1098-1004(1999)13:6<503::AID-HUMU13>3.0.CO;2-F
5. ↑ Romstad A, Kalkanoglu HS, Coskun T, Demirkol M, Tokatli A, Dursun A, Baykal T, Ozalp I, Guldberg P, Guttler F. Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE). Hum Genet. 2000 Dec;107(6):546-53. PMID:11153907