Serotonin and dopamine synthesis in phenylketonuria.

Two regulation systems of the serotonin and dopamine biosynthesis in patients with classical and atypical PKU were investigated. In classical PKU, the serotonin and dopamine biosynthesis is inhibited by high L-phenylalanine in blood and tissues. The dopamine formation in vivo was inhibited by phenylalanine blood concentrations higher than 25 mg/dl: the serotonin formation was inhibited even at a phenylalanine blood concentration of only 8 mg/dl.

Excretion of pterins in phenylketonuria and phenylketonuria variants.

Total urinary biopterin (B), neopterin (Ne) and monapterin (M) were measured in 25 healthy newborns, children and adults, in 49 patients with phenylketonuria (PKU) assumed to be deficient in phenylalanine-4-hydroxylase (PH), in 7 patients with dihydrobiopterin synthetase (DHBS) deficiency and in 4 patients with dihydropteridine reductase (DHPR) deficiency. Excretion of Ne based on creatinine (Ne/C) was 6.6 times higher in healthy newborns than in adults, suggesting a slow maturation of DHBS activity.

["Transitory" phenylketonuria. A permanent deficit].

Three cases are reported with hyperphenylalaninaemia greater than 1.8 micrometer/ml-1 in the neonatal period, becoming tolerant of a normal regime (3 g protein per kg) without plasma levels of phenylalanine exceeding 0.2 to 0.

Atypical phenylketonuria caused by 7, 8-dihydrobiopterin synthetase deficiency.

A patient with atypical phenylketonuria and normal liver dihydropteridine reductase and phenylalanine-4-hydroxylase activities excreted neopterin but not biopterin or dihydrobiopterin in urine. The oral administration of L-sepiapterin (1 mg/kg body weight) lowered serum-henylalanine from 17.1 to 1.

Tetrahydrobiopterin therapy of atypical phenylketonuria due to defective dihydrobiopterin biosynthesis.

A patient with atypical phenylketonuria (defective BH2 synthesis), detected at age 6 months because of severe muscle hypotonia and serum phenylalanine of 20 mg/100 ml, had normal activities of phenylalanine-4-hydroxylase and DHPR in liver biopsy, but only 2% activity in the phenylalanine-4-hyroxylase in vivo test using deuterated phenylalanine. After IV administration of 2.5 mg/kg chemically pure tetrahydrobiopterin bishydrochloride (BH4 .