Alfa-galaktosidaz A eksikliğinde genotip fenotip ilişkisi

Fabry disease results from deficient activity of the enzyme ?-galactosidase (?-Gal A) and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. Fabry disease is inherited in an X-linked manner. The clinical manifestations in heterozygous females range from asymptomatic throughout a normal lifespan to as severe as affected males. Variation in clinical manifestations in heterozygous females is attributed to random X-chromosome inactivation. GLA is the only gene known to be assoiciated with Fabry disease. By this study the variety of GLA mutations in Türkiye will be determined. Also the relationship between genotype and phenotype will be understood. The new patients directed to therapy.After listening ailment of patients and their examination, family pedigrees pictured. By this way carriers and probably new patients were determined. To detect phenotype of the patients some biochemical, haematological studies and radiologic imaging applied them. Also DNA and a-galactosidase A enzyme analysis studied.38 patients from 10 unreleated fabry family recruited for this study. 4 nonsense (p.R220X, p.R227X, p.D255MfsX14, p.K240EfsX9) and 4 missense (p.L36W, p.G258R, p.M42V, p.D266N) mutations and 1 deletion (delE358) determined. Males with the classic form of Fabry disease typically have undetectable enzyme activity and usually develop disease signs and report symptoms in earlier decades of life. The clinical manifestations in heterozygous females were nearly asymptomatic except one of them. Variation in clinical manifestations in heterozygous females is attributed to Lyon hypothesis, or random X-inactivation. The resultant clinical manifestations include acroparesthesias, which usually begin early in childhood, angiokeratoma, hypohidrosis, and the characteristic corneal and lenticular opacities.Most of the affected males described had the classic phenotype. Although the age of onset and/or severity of the manifestations varied, these patients presented with angiokeratoma, hypohidrosis, and acroparesthesias in childhood. This study permit precise carrier detection, genetic counseling, and prenatal diagnosis in these 10 families with this X-linked lysosomal disease. In affected males, a Gal A assays consistently show severely diminished activity in the plasma and leukocytes. In asymptomatic heterozygous females, plasma a Gal A activity may be nearly normal. Tests for GLA gene mutations confirm the diagnosis. Neurological pain, gastrointestinal symptoms, angiokeratoma and corneal dystrophy (cornea verticillata) are particularly common in childhood and their unexplained presence should alert the physician to the possibility of Fabry disease, as should proteinuria of unknown aetiology.Keywords: Fabry Disease, ?-galactosidase A gene, mutation