Tetrahydrobiopterin deficiencies: preliminary analysis from an international survey

Tetrahydrobiopterin deficiency is a rare cause of hyperphenylalaninemic syndromes. The natural history of the disease is characterized by progressive neurologic illness unresponsive to a phenylalanine-restricted diet. Fifty patients have been reported. From the documented cases, the following statements can be made: (1) An incidence of 2% among hyperphenylalaninemic babies can be reasonably estimated. (2) Most patients have high neonatal blood phenylalanine concentrations, but some have only mild elevations. (3) Among the available diagnostic tests, measurement of urine pteridines should be proposed in all hyperphenylalaninemic babies, (4) The tolerance to dietary phenylalanine is generally high. (5) The results of neurotransmitter replacement therapy are encouraging, but treatment should be started within the first month and requires a strict follow-up protocol. Consequently, in every newborn infant with positive Guthrie test results, a rapid investigation of BH4 metabolism should be accomplished in order to differentiate between phenylalanine-hydroxylase deficiencies (phenylketonuria, mild hyperphenylalaninemia, transient hyperphenylalaninemia) and BH4 deficiencies.