Fabry's disease: heterozygous form of different expression in two monozygous twin sisters

A 26-year-old woman presented widespread angiokeratomas predominantly in a swimsuit distribution pattern associated with acroparesthesia in all four limbs. The tentative diagnosis of Fabry's disease (FD) was confirmed by optical and electron-microscopic findings and by appropriate biochemical testing. The work-up showed ocular and renal manifestations of the disease. The monozygous twin sister of the patient was asymptomatic although she was shown to be heterozygous for the enzymatic defect. These 2 cases illustrate the concept of extreme lyonization which can explain observed phenotypic differences in heterozygous females with X-linked hereditary diseases. The father and mother of the patient were shown to be noncarriers of the trait, suggesting de novo mutation in the twin pregnancy. However, biochemical testing for the detection of FD heterozygous females cannot rule out the possibility of the mother being heterozygous with normal enzyme activity.