Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype

Med Clin (Barc). 2014 Jun 6;142(11):497-504. doi: 10.1016/j.medcli.2014.01.032. Epub 2014 Mar 26.

Abstract

Background and objective: Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G.

Patients and methods: Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases.

Results: 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant.

Conclusion: We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time.

Keywords: Fabry; Female; Gravedad; Mujer; Multidisciplinar; Multidisciplinary; Mutación; Mutation; Severity.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Amino Acid Substitution
  • Arrhythmias, Cardiac / etiology
  • Brain / pathology
  • Enzyme Replacement Therapy
  • Eye Diseases / etiology
  • Fabry Disease / complications
  • Fabry Disease / drug therapy
  • Fabry Disease / epidemiology*
  • Fabry Disease / genetics
  • Fabry Disease / pathology
  • Female
  • Genotype
  • Heart Arrest / etiology
  • Heart Transplantation
  • Humans
  • Hypertrophy, Left Ventricular / etiology
  • Kidney / pathology
  • Kidney Diseases, Cystic / etiology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Myocardium / pathology
  • Pedigree
  • Point Mutation*
  • Spain / epidemiology
  • alpha-Galactosidase / genetics*
  • alpha-Galactosidase / therapeutic use

Substances

  • GLA protein, human
  • alpha-Galactosidase