Co-occurrence and contribution of Fabry disease and Klippel-Trenaunay-Weber syndrome to a patient with atypical skin lesions

Fabry disease (FD) is an X-linked recessive inborn error of glycosphingolip id metabolism. Among clinical symptoms, maculopapular skin lesions, known a s angiokeratoma, most often appear on the lower abdomen, scrotum, and thigh s, with a tendency toward bilateral symmetry. A 30-year-old mate patient wa s referred to LIS for evaluation of a complex vascular and cutaneous malfor mation. Skin examination showed numerous angiokeratoma, which had developed only on the right part of the body, with a sharp delineation in the midlin e of the trunk. The diagnosis of FD was confirmed by demonstration of a dec reased alpha -galactosidase A activity, and the patient was shown to be hem izygote for a missense mutation (R342Q) in the alpha -galactosidase A gene (GLA). This mutation was also demonstrated in DNA extracted from fibroblast cultures established from both affected and unaffected skin areas. thus ex cluding the hypothesis of somatic mosaicism or revertant mosaicism. Interes tingly, the diagnosis of Klippel-Trenaunay-Weber syndrome (KTWS) was also m ade, through clinical and radiological investigations. This is the first re port on the association between FD and KTWS. Karyotype analysis was normal. It is likely that the mixed vascular malformations of KTWS affecting capil lary and venous systems have contributed to the unusual angiokeratoma distr ibution pattern observed in the patient.