Patricia A. Barford

Tetrahydrobiopterin deficiency in the neonate: detection, origin and timing

Publisher Summary This chapter discusses the detection, origin, and timing of the tetrahydrobiopterin deficiency in the neonate. The deficiency of tetrahydrobiopterin, an essential cofactor for the formation of the neurotransmitters, dopamine, noradrenaline, and serotonin, is a rare metabolic disorder in the neonate. Children with gross BH4 deficiency in the CNS are unable to form these neurotransmitters and are severely mentally retarded. Not all children who are deficient in BH4 in the CNS have a peripheral defect causing hyperphenylalaninaemia as well. The chapter describes a study of a child who was unable to synthesize BH4 in the CNS, but who could do so in the liver. This child did not have hyperphenylalaninaemia and would not have been detected on the screen. CSF biopterins were, however, much reduced. Severe folate deficiency, either because of malnutrition or because of a genetic defect in folate metabolism, also results in mental retardation without hyperphenylalaninaemia. It has been reported that 5-methyltetrahydrofolate and vitamin B12 enhance BH4 biosynthesis in an in vitro assay system using rat brain preparations. These results demonstrate a clear link between folate, B12, and BH4 biosynthesis. It is, therefore, apparent that a major cause of mental retardation in folate and/or B12 deficiency may be lack of BH4 in the CNS.