THE NATURAL HISTORY OF UNTREATED PHENYLKETONURIA

Fifty‐three cases of untreated classical phenylketonuria are reviewed; 23 of the patients live at home and 30 have been in institutions. Information is given as to the physical and psychiatric features of both groups, with certain differences between them. The natural history of the disease is also discussed. SUMMARY Fifty‐three cases of classical phenylketonuria (untreated) have been reviewed; 23 of the patients live at home and 30 have been in institutions, with two deaths in the latter group. As is to be expected, the more severely affected, with regard to degree of retardation and to neurological and behavioural abnormalities, were found predominantly in the institutional group. Two patients, living at home, were of normal intelligence. Sex distribution was equal, and there was a wide range of ages with, however, only two patients over 50 years of age. This is attributed to less intense diagnosis in older age groups, and to increased institutional mortality with age. Consanguinity was present in two families, and in 43 families there were 148 children with 59 affected (39·9%). The usual clinical features are described; a high incidence of physical congenital defects (35·8%) was found. Most of these were minor. Early symptoms of phenylketonuria included eczema, convulsions, irritability, vomiting, unusual urine odour, aversion to protein foods, and a two‐fold to three‐fold delay in developmental milestones of infancy. A high incidence of neurological defects was also recorded (64·6%), including epilepsy (22·9%), abnormal electroencephalograms (25 out of 30), and “soft” neurological signs such as tremor, ataxia, clonus, etc. Physical growth was often defective, especially in the severe cases. Behavioural abnormalities were found to predominate in the institutional group (averaging 2·2 symptoms per case), being rare in the home group (0·26 per case). Aggressive and destructive behaviour, withdrawn and unresponsive behaviour, and hyperactive behaviour, seemed to be characteristic of phenylketonuria patients when compared with other mental defectives without phenylketonuria; on the other hand, frankly psychotic features, though common in the institutional group (2.3·3%), are also found as commonly in other mentally retarded patients. The natural history of phenylketonuria, and in particular the rate and duration of brain damage, is ill understood. From these retrospective inquiries, some imperfect data suggest that brain damage is maximal in the first six to eight years of life, but that it may continue in some cases into adolescence. This would indicate the need for prolonging dietary treatment beyond the first six to eight years of life, for treated patients. Biochemical features found were those of classical phenylketonuria.