Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life.
OBJECTIVE
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.
Wang
Raymond Y
RY
Medical Genetics Institute, Department of Pediatrics, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, USA.
Lelis
Alicia
A
Mirocha
James
J
Wilcox
William R
WR
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004185:Disability Evaluation; D005080:Exercise Test; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006306:Health Surveys; D006339:Heart Rate; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008499:Medical Records; D009154:Mutation / Q000235:genetics*; D010146:Pain; D010147:Pain Measurement; D011788:Quality of Life; D018434:Sickness Impact Profile; D049951:X Chromosome Inactivation; D000519:alpha-Galactosidase / Q000235:genetics*
D000519:alpha-Galactosidase