Following the diagnosis of Fabry disease in a 45-year-old male, in 31 family members alpha-galactosidase A (alpha-Gal) activity in leucocytes was measured and mutation analysis of the alpha-Gal gene was performed. In the proband, the unique mutation A10523G/N272S in exon 6 was found, which was subsequently detected in seven males (of which one twin) and 10 female subjects. All males showed decreased to absent alpha-Gal A activity in leucocytes, but three out of 10 female subjects had alpha-Gal A activities within normal range. Although all male patients had symptoms of classical Fabry disease, such as acroparesthesias, hypohydrosis and heat-intolerance, there was considerable variability in organ involvement, especially in deterioration of renal function. Detailed studies of large families with Fabry disease may give insight into factors that influence the phenotype of this disorder.

DOI: 10.1038/sj.ejhg.5201184
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