Clinical Manifestations And Mutation Study Of Fabry Disease In Chinese People

Fabry disease is an X linked lysosomal storage disease caused by the deficiency of the lysosomal enzyme alpha-galactosidase A (α-Gal A). The lack ofα-Gal A causes an intracellular accumulation of glycosphingolipida, mainly globotriaosylceramide (GL-3). Organs, including vascular endothelium, heart, brain, and kidneys, were involved, leading to end-stage renal disease (ESRD). Fabry disease encompasses a spectrum of severity, with the classic form representing the most severe phenotype. Less severe cardiac and renal variants of Fabry disease have been recognized in addition to classic form, both of which are characterized by the presence of residualα-Gal A activities, onset in adulthood, and clinical manifestations confined primarily to the myocardium or kidney. The classic form, occurring in males withα-Gal A activity less than 1% of normal mean, usually has its onset in childhood or adolescence with periodic crises of severe pain in the extremities, angiokeratomas and hypohidrosis. Gradual deterioration of renal function to ESRD usually occurs in the third to fifth decades of life. In middle age, most males develop cardiovascular and/or cerebrovascular disease. The most efficient and reliable method for the diagnosis of Fabry disease is the demonstration of deficientα-Gal A, and mutation detection of the GLA gene is the most reliable method for the diagnosis of obligate carrier females and for prenatal diagnosis. Fabry disease was often misdiagnosed in China due to the lack of knowledge and short in confirmation diagnostic approaches. The average interval between onset and final diagnosis was 14 years in two series. This paper aimed at exploring the clinical characteristics of the patients in hoping to improve our knowledge of the disease. We suggested that if a boy with severe episodic pain crises in the extremities, lack of or decreased sweating, and the characteristic skin lesions, angiokeratomas, the activity ofα-Gal A should be assayed or the mutation in his GLA gene should be detected for confirmation diagnosis.17 patients with the classic phenotype of Fabry disease were collected in 16 unrelated Chinese families. DNAs were isolated from affected males and their parents. All seven exons and the flanking intronic sequences of GLA gene were analyzed by sequencing the PCR amplified fragments. 14 types of mutations were identified in 16 probands with 2 genes remaining unknown, including 12 single base substitutions (11 missense and 1 nonsense), 1 single nucleotide deletion and 1 splice site defect. Five mutations were reported previously (e.g. M42V, Rl12C,A292P, R301X and 1188 del C), and 9 were novel mutations (e.g. P40H, D92V,G132R, C174R, G183R, Y216C, L310R, W349R, and IVS1-1G→A).