Nomenclature and laboratory diagnosis of tetrahydrobiopterin deficiencies

Because tetrahydrobiopterin (BH4) deficiency may cause a severe but treatable disease, it became necessary to develop selective screening tests for detection early in infancy. Every newborn with even slight but persistent hyperphenylalaninemia (HPA) should be tested for BH4 deficiency. Such tests have been introduced in many developed countries, but even today older children are invariably detected because of the appearance of clinical symptoms, such as hypotonia of the trunk, hypertonia of the extremities, and often myoclonic seizures, unresponsive to a low-phenylalanine diet. Although according to the literature the frequency of BH4 deficiency is estimated to be 1 to 2 percent among cases with HPA, in some countries, like Turkey and Saudi Arabia the incidence is even higher because of consanguinity.