Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life

Genet Med. 2007 Jan;9(1):34-45. doi: 10.1097/gim.0b013e31802d8321.


Purpose: To determine if there is significant symptomatology in women with heterozygous alpha-galactosidase mutations.

Methods: Data from medical records of the 44 heterozygous females followed at Cedars-Sinai Medical Center were compiled and analyzed for symptoms of Fabry disease. Quality of life data were also analyzed.

Results: Seventy-six percent were referred due to an affected male relative; 76% reported acroparesthesias as their first symptom. A mean of 15.7 years elapsed from onset of first symptoms to the diagnosis. Quality of life, measured by the SF-36 survey, was globally reduced. Pain affected mood and enjoyment of life. Central/peripheral nervous, cardiopulmonary, and renal system manifestations of Fabry disease were present far above that predicted for random X-inactivation of the normal allele. Fatigue, present in 59%, was associated with reduced maximum oxygen consumption (P=0.049); exercise intolerance, present in 83%, was associated with reduced maximal heart rate during exercise testing (P=0.0089). Women diagnosed via family history experienced more angina (P=0.035), decreased vibration sense (P=0.026), and had a worse percentage predicted FEF25-75 (P=0.037) compared to women diagnosed because of symptoms.

Conclusions: This study indicates that the asymptomatic female carrier of Fabry disease is the exception, not the rule: heterozygotes suffer from significant multisystemic disease and reduced quality of life and must be monitored and treated accordingly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Disability Evaluation
  • Exercise Test
  • Fabry Disease / complications
  • Fabry Disease / diagnosis
  • Fabry Disease / genetics*
  • Female
  • Health Surveys
  • Heart Rate
  • Heterozygote*
  • Humans
  • Infant
  • Infant, Newborn
  • Medical Records
  • Mutation / genetics*
  • Pain
  • Pain Measurement
  • Quality of Life*
  • Sickness Impact Profile
  • X Chromosome Inactivation
  • alpha-Galactosidase / genetics*


  • alpha-Galactosidase