Combined tetrahydrobiopterin-phenylalanine loading test in the detection of partially defective biopterin synthesis

Deficiency in the synthesis of biopterin causes neonatal hyperphenylalaninemia. We report a 10-year-old girl of normal appearance with a partial defect in biopterin synthesis, normal intelligence and normal serum phenylalanine levels (95 mumol/l) (1.6 mg/dl). During her 1st year of life serum phenylalanine levels were 250 mumol/l (4 mg/dl) and phenylalanine loading performed at 6 months and 1 year of age was not followed by an increase in serum tyrosine. At 9 years of age she had developed a severely abnormal EEG with focal spike activity but no observable clinical abnormalities. Determination of urinary pterins showed abnormal low levels of biopterin and high levels of neopterin. Phenylalanine loading combined with oral administration of tetrahydrobiopterin (BH4) was followed by a normal increase in serum tyrosine and a normal decrease in serum phenylalanine. Considering the importance of BH4 for the synthesis of dopamine, catecholamines, and serotonin we suggest that these cases should be followed carefully. If neurological symptoms appear, e.g., epilepsy, it may be worthwhile to consider treatment with BH4 and neurotransmitter precursors.