Screening for Fabry disease in patients undergoing dialysis for chronic renal failure in Turkey: identification of new case with novel mutation

Gene. 2013 Sep 15;527(1):42-7. doi: 10.1016/j.gene.2013.05.050. Epub 2013 Jun 10.

Abstract

Background: Chronic renal failure (CRF) is a serious complication of Fabry disease (FD). The aims of the present study were to determine the prevalence of unrecognized FD in Turkish hemodialysis population and to investigate the molecular background.

Method: Primarily, α-galactosidase A (α-Gal A) activity was investigated on DBS in 1136 patients of both sexes who underwent dialysis for CRF in Turkey. The disease was confirmed by analyzing enzyme activity in leukocyte and GLA gene sequencing in all patients in whom α-Gal A level was 40% of normal or less.

Results: Mean age of the patients (44.5% female, 52.5% male) was 56.46±15.85 years. Enzyme activity was found low with DBS method in 12 patients (four males, eight females). Two men, but no women, were diagnosed with FD by enzymatic and molecular analysis. In consequence of genetic analysis of a case, a new mutation [hemizygote c.638C>T (p.P214S) missense mutation in exon 5] was identified, which was not described in literature. Family screening of cases identified six additional cases.

Conclusion: As a result of this initial screening study performed on hemodialysis patients for the first time with DBS method in Turkey, the prevalence of FD was detected as 0.17%. Although the prevalence seems to be low, screening studies are of great importance for detecting hidden cases as well as for identifying other effected family members.

Keywords: CKD; CRF; Chronic renal failure; DBS; DNA; DP; Dialysis; EDTA; FD; Fabry disease; GFR; Gb(3); HD; HGVS; Human Genome Variation Society; LVH; MI; Novel mutation; PCR; PD; RF; Screening; alpha-galactosidase A; chronic kidney disease; chronic renal failure; deoxyribonucleic acid; dialysis patients; dried blood samples; ethylenediaminetetraacetic acid; globotriaosylceramide; glomerular filtration rate; hemodialysis; left ventricular hypertrophy; myocardial infarction; peritoneal dialysis; polymerase chain reaction; renal failure; α-Gal A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Case-Control Studies
  • DNA Mutational Analysis
  • Fabry Disease / diagnosis
  • Fabry Disease / epidemiology
  • Fabry Disease / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Testing
  • Hemizygote
  • Humans
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Mutation, Missense
  • Pedigree
  • Point Mutation
  • Prevalence
  • Renal Dialysis
  • Turkey / epidemiology
  • Young Adult
  • alpha-Galactosidase / genetics*

Substances

  • GLA protein, human
  • alpha-Galactosidase