Hyperphenylalaninemia due to dihydropteridine reductase deficiency

Hyperphenylalaninemia due to dihydropteridine reductase deficiency is a rare genetic disorder characterized by an increased level of the amino acid phenylalanine in the blood. This condition is a form of hyperphenylalaninemia, specifically caused by a deficiency in the enzyme dihydropteridine reductase (DHPR). DHPR is essential for the metabolism of phenylalanine, and its deficiency disrupts this process, leading to the accumulation of phenylalanine and other metabolites in the body. This disorder falls under the category of phenylketonuria (PKU) and is also related to tetrahydrobiopterin (BH4) deficiency disorders, as DHPR is involved in the regeneration of BH4, a cofactor for phenylalanine hydroxylase and other enzymes.

Symptoms and Diagnosis

The symptoms of hyperphenylalaninemia due to dihydropteridine reductase deficiency can vary widely among affected individuals. Early signs often include intellectual disability, microcephaly (small head size), seizures, and developmental delays. Without prompt treatment, the condition can lead to severe neurological complications, including movement disorders, psychiatric symptoms, and potentially life-threatening complications.

Diagnosis is typically made through newborn screening, which can detect elevated levels of phenylalanine in the blood. Confirmatory tests include measuring the activity of dihydropteridine reductase in blood or tissue samples. Genetic testing can also identify mutations in the QDPR gene, which encodes the DHPR enzyme.

Treatment

Treatment of hyperphenylalaninemia due to dihydropteridine reductase deficiency is complex and requires a multidisciplinary approach. The primary goal is to normalize phenylalanine levels in the blood through dietary management, which involves a low-phenylalanine diet. Additionally, patients may require supplementation with L-DOPA and 5-hydroxytryptophan (5-HTP), as the deficiency affects the synthesis of the neurotransmitters dopamine and serotonin.

Prognosis

The prognosis for individuals with hyperphenylalaninemia due to dihydropteridine reductase deficiency varies. Early diagnosis and treatment can improve outcomes significantly, but even with treatment, some individuals may experience ongoing neurological problems or developmental delays.

Epidemiology

Hyperphenylalaninemia due to dihydropteridine reductase deficiency is extremely rare, with only a small number of cases reported worldwide. It is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.

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