Dihydropteridine Reductase (DHPR) Deficiency
Dihydropteridine reductase (DHPR) deficiency manifests in a variety of phenotypes, all with hyperphenylalaninemia. The clinical presentation is similar to that observed with PTS deficiency. Without folinic acid to restore methyltetrahydrofolate status in the CNS, these patients can have progressive calcification of the basal ganglia and subcortical regions, despite treatment with BH4 and neurotransmitter precursors.3 A juvenile variant has been reported in which siblings were developmentally normal until 6 years of age, at which time they developed progressive encephalopathy, epilepsy, and pyramidal, cerebellar, and extrapyramidal features on clinical examination.
Diagnosis can be confirmed by the pattern of urine pterins, and documentation of abnormal DHPR activity in skin fibroblasts. Phenylalanine loading tests are abnormal, and phenylalanine status improves or normalizes with BH4 supplementation. CSF neurotransmitter and pterin analysis reveals reduced HVA, 5-HIAA, decreased or normal BH4, and elevated dihydrobiopterin levels.
