SUMMARY Heterozygote detection for angiokeratoma corporis diffusum (Anderson-Fabry disease, ACD), an X-linked disorder of glycosphingolipid metabolism, was examined using a-galactosidase activity, an a-galactosidase/fl-galactosidase activity ratios (a/f ratio) in leucocytes, plasma, and hair follicles. For leucocytes, 22 obligate heterozygotes, 25 suspected heterozygotes, and 47 control subjects were studied, while for plasma, the groups were 17 obligate heterozygotes and 35 controls. The a/fl ratio in plasma and leucocytes was clearly a better discriminator between obligate heterozygotes and controls than a-galactosidase activity alone, but still failed to detect 3 obligates with leucocytes and 2 with plasma. Discrimination was not improved by joint use of plasma and leucocyte a/fl ratios, but was improved by measurement of hair-follicle a/f ratios. The interdecile range of log (a-galactosidase/fl-galactosidase activity) in 20 hair follicles from each of 4 obligate and 7 suspected heterozygotes was clearly different from 11 control subjects. Accordingly, for rapid screening for carriers of ACD, we recommend use of leucocyte or plasma a/f ratios which should detect > 85% of heterozygotes. When results are equivocal, and ancillary information suggests heterozygous status, the more time-consuming measurement of hair-follicle a/f ratios is a useful additional test.

SUMMARY 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 (aged 36 and 47) had evidence of significant renal disease. Electrocardiograms showed abnormally short PR intervals in 4, and right ventricular conduction disturbances in 5.

SUMMARY: 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