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Dihydropteridine reductase deficiency

Orpha number ORPHA226
Synonym(s) Hyperphenylalaninemia due to dihydropteridine reductase deficiency
PKU type 2
Phenylketonuria type 2
Prevalence Unknown
Inheritance Autosomal recessive
Age of onset Infancy
  • E70.1
  • C0268465
  • C2936906
  • C537896
MedDRA -
  • 58256000


Dihydropteridine reductase (DHPR) deficiency, an autosomal recessive genetic disorder, is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterine deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases. DHPR deficiency should be suspected in all infants with a positive neonatal screening test for phenylketonuria, especially when hyperphenylalaninemia is moderate. DHPR activity can be measured by means of a technique adapted to dry blood samples. When left untreated, DHPR deficiency leads to neurological signs at age 4 or 5 months, although clinical signs are often obvious from birth. The principal symptoms include: psychomotor retardation, tonicity disorders, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficult swallowing. The treatment attempts to bring phenylalaninemia levels back to normal (diet with restricted phenylalanine intake or prescription of tetrahydrobiopterin) and to restore normal monoaminergic neurotransmission by administering precursors (L-dopa/carbidopa and 5-hydroxytryptophane). Folic acid intake prevents progressive deficits of cerebral folates, while antifolates, such as cotrimoxazole are dangerous.

Expert reviewer(s)

  • Pr Jean-Louis DHONDT

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Detailed information

Review article
  • FR (2005,pdf)
  • EN (2005,pdf)
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