Different phenotypic expression in relatives with Fabry disease caused by a W226X mutation

Two male relatives with Fabry disease presented striking differences in cli nical symptoms and age of onset. The propositus had retarded statural growt h and skeletal dysplasia while his nephew suffered mainly from aggravating acroparesthesia and celiac disease. Fabry disease is an X-linked inborn err or of glycosphingolipid metabolism resulting from deficient activity of the lysosomal hydrolase alpha-galactosidase A (alpha-Gal A) enzyme. The alpha- Gal A gene is located at Xq22.1. Efforts to establish genotype-phenotype co rrelations have been limited because most patients have private mutations, In previous clinical studies performed in families with Fabry disease, mark ed differences in phenotype are described between affected relatives. This family also demonstrates the difficulty in predicting the clinical phenotyp e in patients and relatives with the same alpha-Gal A mutation. Furthermore , in the absence of a family history, the diagnosis may be easily missed. ( C) 1999 Wiley-Liss, Inc.