Effect of dietary phenylalanine restriction on visual attention span in mentally retarded subjects with phenylketonuria.

An ABA within-subject study design was used to assess the effect of dietary phenylalanine restriction on the visual attention span of three mentally retarded males (9, 15, and 21 years old) with phenylketonuria. Visual attention span was measured by recording the amount of time the subjects visually fixated pictures projected on a screen according to a standardized test protocol. After 4-6 weeks of baseline testing (A-phase), each subject was placed on a phenylalanine-restricted diet, designed to maintain plasma phenylalanine levels at 0.3-0.9 mM, for 8-14 weeks (B-phase). A return to baseline phenylalanine intake (A-phase) was achieved by surreptitiously adding sufficient L-phenylalanine to the therapeutic diets to increase plasma concentrations of the amino acid to pretreatment levels. Diet treatment (B-phase) was associated with highly significant improvements in visual attention span in two subjects (multivariate analysis of variance, P less than 0.001); the third subject, the most retarded, showed no effect. No objectively demonstrable change in behavior was documented in any subject. However, the results support the view that phenylalanine toxicity extends beyond early childhood and that some component of the toxicity is reversible, even in severely retarded patients with phenylketonuria.

Angiokeratoma corporis diffusum (Anderson-Fabry disease) in a single large family in Nova Scotia.

Eighteen males, 17 of whom were members of a single family, affected with angiokeratoma corporis diffusum were examined in detail to determine the extent of clinical variation of the expression of what was almost certainly the same X-linked mutation in each. The commonest symptom was episodic bouts of severe, painful dysaesthesia in hands and feet. This was a major complaint of 12, a minor complaint of 5, and absent in 1. In over half the subjects, the skin rash that is considered a characteristic sign of the disease was absent or inconspicuous. All exhibited mild clubbing of fingers and toes, and 15 showed variable limitation of active and passive extension of the 5th fingers bilaterally. Only 2 (age 36 and 47) had evidence of significant renal disease. Electrocardiograms showed abnormally short PR intervals in 4, and right ventricular conduction disturbances in 5. Echocardiograms on 9 showed no evidence of myocardial dysfunction. The marked variation of the expression of some features of the disease indicates that the clinical expression of the mutation is likely to be subject to considerable genetic or environmental modification in each individual.

Failure to correct the metabolic defect by renal allotransplantion in Fabry's disease.

Plasma neutral glycolipid levels and plasma and leukocyte alpha-galactosidase activities were measured serially before and after renal allotransplantation in two men, aged 47 and 45 years, with renal failure due to Fabry's disease. The patients were followed posttransplantation for 92 and 64 weeks, respectively. No significant elevation of plasma or leukocyte alpha-galactosidase activities above levels in untreated men with Fabry's disease or decrease in the levels of trihexosyl ceramide was observed in either patient. The results do not support the use of renal allotransplantation for enzyme replacement in Fabry's disease.