, Volume 77, Issue 2, pp 168-171

Hyperphenylalaninemia due to deficiency of 6-pyruvoyl tetrahydropterin synthase

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We have identified deficient biopterin synthesis in four probands and one sib with persistent postnatal hyperphenylalaninemia. The metabolic findings were associated with a benign clinical presentation and normal biopterin level in cerebrospinal fluid in the newborn period, indicating the peripheral (hepatic) form of this autosomal recessive phenotype. Impaired development was apparent at 3 months in one proband not treated early. Treatment with oral tetrahydropterin restored adequate phenylalanine hydroxylase activity; it also maintained or improved CNS function. The deficient enzyme in these subjects is 6-pyruvoyl tetrahydropterín synthase (PTS). Erythrocyte activity of PTS in homozygotes (or compound heterozygotes) is <10% of normal. Heterozygotes have 20%–50% of normal PTS activity (enzyme phenotype), a finding compatible with a range of gene dosage effects, some abnormal. The metabolic phenotype in heterozygotes (urine biopterin excretion) did not correlate with erythrocyte PTS activity. The complex relationship between erythrocyte PTS activity, and biopterin synthesis in these families indicates genetic heterogeneity at the PTS locus.

Professor Niederwieser has unfortunately died since the paper was accepted