Unsuccessful treatment of phenylketonuria with tyrosine

Abstract

ON E of the earliest questions in the treatment of phenylketonuria was whether the severe mental retardation characteristic of this disorder was caused by phenylalanine accumulation or by tyrosine deficiency. Although early therapy with a diet low in phenylalanine and supplemented with tyrosine is effective in preventing mental retardation in PKU, 1, ~ the role of a tyrosinesupplemented diet alone has not been evaluated. We present the case of a child born in 1967 whose parents elected 1o have him treated with tyrosine supplementation rather than with phenylalanine restriction. CASE REPORT The patient was the product of an uncomplicated term pregnancy, labor, and delivery in a gravida 3, para 2, 25-year-old mother. Birth weight was 4.3 kg an d the Apgar score was 10 at 5 minutes. The neonatal course was uncomplicated. However, plasma phenylatanine concentrations at 3 and 10 days of age were 1,400 and 3,030 ~M, respectively (normal range 26 to 61 /~M). Plasma tyros!no concentration was 70/xM at 10 days of age (normal range 31 to 71 /~M). The child was placed on the standard phenylalanine-restricted diet for two weeks. However, the parents noted the child to be irritable and lethargic and requested that the diet be terminated. They questioned whether another form of therapy might be available, and consented to a trial of tyrosine supplementation alone, c-Tyrosine, as a free base, was given with meals at a dose of 200 mg/day. Plasma tyrosine concentration rose to 214 ~M. Tyrosine supplementation was continued until 4 years of age at doses ranging from 200 to 300 mg/day. During this time plasma phenylalanine concentrations ranged from 1,370 to 3,818 tsM and plasma tyrosine values from 62 to 219/~M. Therapy was discontinued at four years when it became apparent that the child was severely retarded. Developmental milestones were delayed from infancy. Motor skills were always less affected than were language skills. The