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Normal Function
The QDPR gene provides instructions for making an enzyme called quinoid dihydropteridine reductase. This enzyme helps carry out one step in the chemical pathway that recycles a molecule called tetrahydrobiopterin (BH4).
Tetrahydrobiopterin plays a critical role in processing several protein building blocks (amino acids) in the body. For example, it works with the enzyme phenylalanine hydroxylase to convert an amino acid called phenylalanine into another amino acid, tyrosine. Tetrahydrobiopterin is also involved in reactions that produce chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Because it helps enzymes carry out chemical reactions, tetrahydrobiopterin is known as a cofactor.
When tetrahydrobiopterin interacts with enzymes during chemical reactions, the cofactor is altered and must be recycled to a usable form. Quinoid dihydropteridine reductase is one of two enzymes that help recycle tetrahydrobiopterin in the body.
Health Conditions Related to Genetic Changes
Tetrahydrobiopterin deficiency
More than 30 mutations in the QDPR gene have been found to cause tetrahydrobiopterin deficiency. When this condition results from QDPR gene mutations, it is known as dihydropteridine reductase (DHPR) deficiency. DHPR deficiency accounts for about one-third of all cases of tetrahydrobiopterin deficiency.
Most QDPR gene mutations change single amino acids in quinoid dihydropteridine reductase, although some mutations insert small amounts of DNA into the QDPR gene or disrupt the way the gene's instructions are used to make the enzyme. Changes in quinoid dihydropteridine reductase greatly reduce or eliminate the enzyme's activity. Without enough of this enzyme, tetrahydrobiopterin is not recycled properly. As a result, this cofactor is not available to participate in chemical reactions such as the conversion of phenylalanine to tyrosine. If phenylalanine is not converted to tyrosine, it can build up to toxic levels in the blood and other tissues. Nerve cells in the brain are particularly sensitive to phenylalanine levels, which is why excessive amounts of this substance can cause brain damage.
Additionally, a reduction in quinoid dihydropteridine reductase activity disrupts the production of certain neurotransmitters in the brain. Because neurotransmitters are necessary for normal brain function, changes in the levels of these brain chemicals contribute to intellectual disability in people with DHPR deficiency.
More About This Health ConditionOther Names for This Gene
- DHPR
- DHPR_HUMAN
- Dihydropteridine reductase
- PKU2
- SDR33C1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- 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. doi: 10.1002/(SICI)1098-1004(1998)12:43.0.CO;2-C. Citation on PubMed
- Longo N. Disorders of biopterin metabolism. J Inherit Metab Dis. 2009 Jun;32(3):333-42. doi: 10.1007/s10545-009-1067-2. Epub 2009 Feb 9. Citation on PubMed
- Ponzone A, Spada M, Ferraris S, Dianzani I, de Sanctis L. Dihydropteridine reductase deficiency in man: from biology to treatment. Med Res Rev. 2004 Mar;24(2):127-50. doi: 10.1002/med.10055. Citation on PubMed
- 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. doi: 10.1007/s004390000407. Citation on PubMed
- Shintaku H. Disorders of tetrahydrobiopterin metabolism and their treatment. Curr Drug Metab. 2002 Apr;3(2):123-31. doi: 10.2174/1389200024605145. Citation on PubMed
- Thony B, Auerbach G, Blau N. Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J. 2000 Apr 1;347 Pt 1(Pt 1):1-16. Citation on PubMed or Free article on PubMed Central
- Thony B, Blau N. Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. Hum Mutat. 2006 Sep;27(9):870-8. doi: 10.1002/humu.20366. Citation on PubMed
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