Oral phenylalanine loading test for the diagnosis of dominant guanosine triphosphate cyclohydrolase 1 deficiency

To evaluate the usefulness of Phe loading test in patients for the diagnosis of guanosine triphosphate cyclohydrolase 1 deficiency (GTPCH). We studied one family composed of 13 members harbouring the Q89X mutation in the GTPCH gene, a non-related pediatric patient with GTPCH deficiency and 8 pediatric controls. 100 mg/kg of l-phenylalanine was orally administered, and blood spot samples were taken at baselines 1, 2, 4 and 6 h post-load. Two out of 7 pediatric patients showed a phenylalanine/tyrosine ratio higher than the previously reported cut-off value of 5.25 at 4 h, while 6 of the 7 adult patients showed a higher value. The only adult patient with a phenylalanine/tyrosine ratio below 5.25 at 4 h was asymptomatic. A cut-off value of 5.25 seems reliable for interpreting Phe loading test in adult patients with GTPCH deficiency, although a lower value should be established for pediatric patients.