Urinary globotriaosylceramide excretion correlates with the genotype in children and adults with Fabry disease

摘要: Fabry disease is a complex, multisystemic and clinically heterogeneous disease, in which the urinary excretion of globotriaosylceramide (Gb3), principal substrate deficient enzyme, alpha-galactosidase A, more prominent than increased concentrations lipid plasma affected hemizygotes heterozygotes. We have developed validated simultaneous analysis Gb3 creatinine 2.6-min run using filter paper discs saturated with urine analyzed by LC-MS/MS. Using this method, we studied relationship between levels total Gb3/creatinine four types mutations GLA gene (missense, nonsense, frameshift, splice-site defects) 32 children 78 adult patients disease. Forty-one were treated enzyme replacement therapy 69 untreated. Our results show that mean recoveries from standards 91% 97%, respectively, precision, reproducibility, linearity within acceptable ranges. Statistical independent variables sex, age, treatment showed mutation factor has statistically significant impact on (p = 0.0007). This means adults are directly related to mutations. The same correlation was found for sex < 0.0001) 0.0011). In conclusion, 35 110 patients.