Dihydropteridine reductase deficiency

Alternate Names

DHPR deficiency; Hyperphenylalaninemia, BH-4-deficient, C; Hyperphenylalaninemia due to dihydropteridine reductase deficiency; Phenylketonuria type 2; Quinoid dihydropteridine reductase deficiency; QDPR deficiency; PKU type 2

Rare disease

Dihydropteridine reductase deficiency (DHPR) is a rare disease caused by a severe form of hyperphenylalaninemia (high levels of the amino acid phenylalanine in the blood) due to impaired renewal of a substance known as tetrahydrobiopterin (BH4).

Tetrahydrobiopterin normally helps process several amino acids, including phenylalanine, and it is also involved in the production of neurotransmitters. If little or no tetrahydrobiopterin is available to help process phenylalanine, this amino acid can build up in the blood and other tissues and the levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid are also decreased.

Cause

DHPR deficiency is caused by mutations in the QDPR gene.

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.

Inheritance

Autosomal recessive inheritance, a 25% chance

It is inherited in an autosomal recessive manner.

Signs and symptoms

Neurological symptoms such as psychomotor delay, low muscle tone (hypotonia), seizures, abnormal movements, too much salivation, and swallowing difficulties.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Dysphagia(Poor swallowing)
• Global developmental delay
• Intellectual disability(Mental deficiency)
• Microcephaly(Abnormally small skull)

Diagnosis

Prenatal Diagnosis

Dahl et al. (1987, 1988) showed that RFLPs of the DHPR locus could be used for prenatal diagnosis.

The patients were detected at neonatal screening for hyperphenylalaninemia or upon the development of neurologic symptoms. A mutation screen of the entire open reading frame and all splice sites of the QDPR gene identified 10 different mutations.

Treatment

Treatment should be started as soon as possible and includes tetrahydrobiopterin BH4 supplementation usually combined with a diet without phenylalanine, folate supplementation, and specific medications to restore the levels of neurotransmitters in the brain. Latest articles - Dihydropteridine reductase deficiency

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Dihydropteridine reductase deficiency on Wikipedia

• Wikipedia's article on Dihydropteridine reductase deficiency

NIH genetic and rare disease info

• NIH info on Dihydropteridine reductase deficiency

Dihydropteridine reductase deficiency is a rare disease.

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