THE VARIABILITY IN MANIFESTATIONS OF UNTREATED PATIENTS WITH PHENYLKETONURIA (PHENYLPYRUVIC ACIDURIA)

Abstract

One hundred six cases of phenylketonuria have been surveyed in 11 institutions in New England and Eastern Canada. Data not previously available (and of some degree of uncertainty as to reliability) are presented as to the ages at which patients with phenylketonuria achieve the ability to sit unsupported, to walk independently, and to say recognizable words. A small number of patients achieve these steps at reasonably near the normal age and the degree of variability is such that early developmental timetables should not be overemphasized in interpreting possible effects of any treatment of the disease. Both eczema and seizures are proportionately more frequent in severely retarded patients with phenylketonuria than in those with lesser degrees of intellectual defect. If present at the time an experimental treatment is instituted, they would provide more objective evidence of possible benefit. Electroencephalograms were abnormal in 79% of patients for whom tracings were available and would provide one means of evaluating plans of treatment even in the absence of seizures. While the majority of these patients have blue eyes and blond hair, there is enough evidence to suggest a tendency to darkening of the hair with age that this also should be used with caution in evaluation of treatment. Frequencies of various neurologic manifestations are presented, including unusual hand posturing, tremor, hyperreflexia, clonus and spasticity. These are all variable enough that a reasonably positive diagnosis [See FIG. 2. in Source Pdf.] by physical examination is not possible, and further, they are not well adapted to evaluation of treatment. The distribution of intelligence quotients in patients with phenylketonuria appears to follow a continuous curve and to include a small number of persons with borderline normal or better intelligence. In assessing the effect of any treatment, it is unwarranted to ascribe to that treatment the attainment of borderline normal intellectual levels that may be reached by small numbers of patients, especially if originally tested in infancy or early childhood. The effect of any therapy can be adequately evaluated only by comparing changes in a number of treated patients with phenylketonuria, with changes in comparable control patients, selected on the basis of intelligence, age, physical accomplishments, and status with respect to hair color, eczema, convulsive seizures and electroencephalographic findings.