Diagnostic and therapeutic aspects of dihydrobiopterin deficiency

The first Scandinavian hyperphenylalaninaemic patient with a cofactor deficiency is described. By neonatal screening the Guthrie test showed a serum phenylalanine of 302 mumol/1 (5 mg/dl), which at age 6 weeks had fallen to high normal values. At age 5 1/2 months the serum phenylalanine was around 2000 mumol/1 and the child presented with severe neurological symptoms. The diagnosis of defect dihydrobiopterin biosynthesis was made by high performance liquid chromatography of the urine. Loading tests followed by daily treatment of the missing cofactor was able to keep the serum phenylalanine in the normal level. Because of persisting, yet diminishing neurological symptoms neurotransmitter treatment was started. Breast feeding as the cause of the low neonatal levels of serum phenylalanine and the late start of clinical symptoms is proposed and the importance of screening all hyperphenylalaninaemic newborns for defect biopterin metabolism is stressed.