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. Newborns excreted more Ne than B and adults more B than Ne (32 and 72% B of the sum of B + Ne, respectively). In all cases, excretion of M was 4-15% of that of Ne. PH deficient patients excreted more B and Ne than healthy controls and again, newborns more than older children. In individual patients, excretion of
pterins correlated with
phenylalanine (Phe) concentration in plasma; plasma Phe of different patients did not correlate well with excretion of
pterins. In PKU variants with deficiency of
tetrahydrobiopterin (BH4), extreme
pterin patterns were observed: in
DHBS- and DHPR-deficient patients, less than 3.5 and more than 81% B were found, respectively. All 30 samples from these patients investigated could be distinguished from those of PH-deficient patients and controls by a two-dimensional plot of % B versus B/C. Thus it seems likely that PKU variants due to
BH4 deficiency could be detected early and differentiated by measurement of urinary B, Ne and C. This was exemplified already in one case. - In urine of patients with
DHBS deficiency, high concentrations of
3'-hydroxysepiapterin were found in addition to Ne.