A novel mutation of α-galactosidase A gene causes Fabry disease mimicking primary erythromelalgia in a Chinese family

Purpose: Fabry disease is an X-linked genetic disorder caused by the mutations of alpha-galactosidase A (GLA, MIM 300644) gene presenting with various clinical symptoms including small-fiber peripheral neuropathy and limb burning pain. Here, we reported a Chinese pedigree with the initial diagnosis of primary erythromelalgia in an autosomal dominant (AD)-inherited pattern. Methods: Mutation analysis of SCN9A and GLA genes by direct sequencing and functional analysis of a novel mutation of GLA in cells were performed. Results: Our data did not show any pathological mutations in SCN9A gene; however, a novel missense mutation c. 139T> C (p. W47R) of GLA was identified in amale proband as well as two female carriers in this family. Enzyme assay of alpha-galactosidase A activity showed deficient enzyme activity inmale patients and female carriers, further confirming the diagnosis of Fabry disease. Finally, a functional analysis indicated that the replacement of the 47th amino acid tryptophan (W47) with arginine (W47R) or glycine (W47G) led to reduced activity of a-galactosidase A in 293T cells. Therefore, these findings demonstrated that the novel mutation p. W47R of GLA is the cause of Fabry disease. Conclusions: Because Fabry disease and primary erythromelalgia share similar symptoms, it is a good strategy for clinical physicians to perform genetic mutation screenings on both SCN9A and GLA genes in those patients with limb burning pain but without a clear inheritant pattern.