Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry.
Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A deficiency. The Fabry Registry is a global clinical effort to collect longitudinal data on FD. In the past, most "carrier" females were usually thought to be clinically unaffected. A systematic effort has been made to enroll all FD females, regardless of symptomology. Of the 1077 enrolled females in the Registry, 69.4% had symptoms and signs of FD. The median age at symptom onset among females was 13 years, and even though 84.1% had a positive family history, the diagnosis was not made until a median age of 31 years. Twenty percent experienced major cerebrovascular, cardiac, or renal events, at a median age of 46 years. Among adult females with estimated glomerular filtration rate (eGFR) data (N=638), 62.5% had an eGFR <90 ml/min/1.73 m2 and 19.0% had eGFR <60 ml/min/1.73 m2. Proteinuria 300 mg/day was present in 39.0% of females, and 22.2% had >1 gram/day. Quality of life (QoL), as measured by the SF-36((R)) survey, was impaired at a later age than in males, but both genders experience significantly impaired QoL from the third decade of life onward. Thus, females with FD have a significant risk for major organ involvement and decreased QoL. Females should be regularly monitored for signs and symptoms of FD, and considered for enzyme replacement therapy.
Wilcox
William R
WR
Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd. SSB, Los Angeles, CA 90048, USA. william.wilcox@cshs.org
Oliveira
João Paulo
JP
Hopkin
Robert J
RJ
Ortiz
Alberto
A
Banikazemi
Maryam
M
Feldt-Rasmussen
Ulla
U
Sims
Katherine
K
Waldek
Stephen
S
Pastores
Gregory M
GM
Lee
Philip
P
Eng
Christine M
CM
Marodi
Laszlo
L
Stanford
Kevin E
KE
Breunig
Frank
F
Wanner
Christoph
C
Warnock
David G
DG
Lemay
Roberta M
RM
Germain
Dominique P
DP
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002318:Cardiovascular Diseases / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000235:genetics; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006579:Heterozygote; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D010641:Phenotype; D011788:Quality of Life; D012042:Registries; D012727:Sex Characteristics; D014481:United States; D000519:alpha-Galactosidase / Q000235:genetics / Q000627:therapeutic use
D000519:alpha-Galactosidase