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J Inherit Metab Dis ; 24(3): 352-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11486900

ABSTRACT

Four neonates with a positive phenylalanine screening test (Phe concentrations between 258 and 1250 micromol/L) were investigated further to differentiate between phenylalanine hydroxylase (PAH) deficiency and variant hyperphenylalaninaemia (HPA) forms. In patients 1 and 2 a tetrahydrobiopterin (BH4) load caused a significant decrease of the plasma Phe levels. A combined phenylalanine/BH4 loading test was performed in patients 2, 3 and 4. In the latter two patients, plasma Phe concentrations completely normalized within 8 h after the BH4 load (20 mg/kg). Basal urinary pterins were normal in all four patients. The activity of dihydropteridine reductase (DHPR) was normal in patients 1, 2 and 3 and 50% of control values in patient 4 (not in the range of DHPR-deficient patients). In patient 3 a subsequent phenylalanine loading test with concomitant analysis of plasma biopterins revealed a normal increase of biopterin, excluding a BH4 biosynthesis defect. Pterins and neurotransmitter metabolites in CSF of patients 1, 3 and 4 were normal. DNA mutations detected in the PAH gene of patients 1-4 were A313T, and L367fsinsC; V190A and R243X; A300S and A403V; R241C and A403V. The results are suggestive for mutant PAH enzymes with decreased affinity for the cofactor BH4.


Subject(s)
Biopterins/analogs & derivatives , Biopterins/therapeutic use , Phenylalanine Hydroxylase/deficiency , Biopterins/blood , DNA Mutational Analysis , Diagnosis, Differential , Dihydropteridine Reductase/metabolism , Female , Humans , Infant, Newborn , Kinetics , Mutation , Netherlands , Phenylalanine/blood , Phenylalanine Hydroxylase/genetics , Polymorphism, Single-Stranded Conformational , Pterins/cerebrospinal fluid , Pterins/urine
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