Clinical characteristics and mutation spectrum of GLA in Korean patients with Fabry disease by a nationwide survey: Underdiagnosis of late-onset phenotype

Medicine (Baltimore). 2017 Jul;96(29):e7387. doi: 10.1097/MD.0000000000007387.

Abstract

Fabry disease is a rare X-linked lysosomal storage disorder caused by an α-galactosidase A deficiency. The progressive accumulation of globotriaosylceramide (GL-3) results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. This study investigated the phenotypic and molecular spectra of GLA mutations in Korean patients with Fabry disease using a nationwide survey.This study included 94 patients from 46 independent pedigrees: 38 adult males, 46 symptomatic females, and 10 pediatric males. Each diagnosis was based on an enzyme assay and GLA gene mutation analysis.The mean age at presentation was 24 years (range, 5-65 years); however, the diagnoses were delayed by 21 ± 19 years after the onset of symptoms. Those patients with late-onset Fabry disease were diagnosed by family screening or milder symptoms at a later age. Forty different mutations were identified: 20 missense (50%), 10 nonsense (25%), 8 frameshift (20%), and 2 splice site (5%) mutations. Five of them were novel. IVS4+919G>A (c.936+919 G>A) was not detected among the 6505 alleles via newborn screening using dried blood spots. Enzyme replacement therapy (ERT) was performed in all the males and pediatric patients, whereas 75% of the symptomatic females underwent ERT for 4.2 ± 3.6 years.This study described the demographic data, wide clinical spectrum of phenotypes, and GLA mutation spectrum of Fabry disease in Korea. Most of the patients had classical Fabry disease, with a 4 times higher incidence than that of late-onset Fabry disease, indicating an underdiagnosis of mild, late-onset Fabry disease.

MeSH terms

  • Adolescent
  • Age of Onset
  • Aged
  • Child
  • Child, Preschool
  • Diagnostic Errors
  • Enzyme Replacement Therapy
  • Fabry Disease / diagnosis
  • Fabry Disease / drug therapy
  • Fabry Disease / epidemiology*
  • Fabry Disease / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • Incidence
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation*
  • Neonatal Screening
  • Phenotype
  • Republic of Korea / epidemiology
  • Surveys and Questionnaires
  • Treatment Outcome
  • Young Adult
  • alpha-Galactosidase / genetics*

Substances

  • GLA protein, human
  • alpha-Galactosidase