Phenylalanine-restricted diets in the treatment of phenylketonuria.

Phenylalanine restriction has been used in the treatment of the metabolic and mental disorders of phenylketonuria with conflicting results. Bickel, Gerrard and Hickmans (1953) reported the first successful treatment of a child aged 31 who was observed for 12 months in hospital and at home. The biochemical abnormality of phenylpyruvic acid in the urine was corrected in this patient, but evidence of prolonged biochemical normality was not given, and, although the improvement in her mental condition was promising, prolonged psychological tests were not done. Woolf, Griffiths and Moncrieff (1955) reported studies of three further children for six to nine months, in whom satisfactory mental and biochemical improvements were found. Less conclusive advance in the mental state was observed by Armstrong and Tyler (1955) despite apparently normal biochemistry in the serum and urine in five children aged 9 months to 41 years. Confusion also persists regarding the longer-term effects of phenylalanine restriction on the physical, biochemical and mental states of these children and adequate criteria of control and assessment have not been clearly defined. Some workers have used synthetic diets with pure amino-acids; others have given casein hydrolysates low in phenylalanine as the source of nitrogen. The ages of the children treated have varied considerably, and the initial degree of mental defect has not always been clearly described. It is the purpose of the present paper to confirm that apparent biochemical normality can be obtained, with normal growth and physical development for long periods, using diets very severely limited in phenylalanine, and to assess critically the mental progress attained in a group of six children treated for up to three years with such diets.