Renal Implications

Renal pathology in Fabry disease worsens with age.1 Studies on kidney involvement in Fabry disease demonstrate that multiple cell types are affected by GL-3 deposition, and these include glomerular endothelial cells, mesangial cells, interstitial cells, distal tubules, and podocytes.1,2

Renal impairment, as indicated by the presence of microalbuminuria and proteinuria, often begins in the second to third decades of life and leads to progression to Fabry nephropathy and ultimately end-stage renal disease, a major cause of morbidity and mortality.3,4

The prevalence of Fabry disease is high among patients with end-stage renal disease, with an incidence in European patients undergoing dialysis of approximately 1 in 5,300 and US patients undergoing dialysis of approximately 1 in 6,000.5

Cardiovascular Implications

Cardiac changes in Fabry disease include infiltrative hypertrophic cardiomyopathy (which is most often identified as left ventricular hypertrophy [LVH]), as well as conduction abnormalities; of these, LVH is one of the strongest predictors for cardiac events.6-8 Findings of The Fabry Registry* showed that cardiovascular disease was the main cause of death of patients, with 53.6% of male deaths and 50.0% of female deaths attributable to this cause.3

Cardiac symptoms appear approximately 10 years earlier in males than in females but are now understood to affect both sexes, with approximately 90% of patients being affected by cardiomyopathy.6,9 Cardiac involvement is often present early in life but may not be detected clinically until the third or fourth decade.7

As the disease progresses, cardiac symptoms and cardiomyopathy develop, as indicated by myocardial fibrosis, which, in end-stage patients, can result in congestive heart failure and death.10

Rhythm and conduction abnormalities are also common in patients with Fabry disease and are a source of morbidity and mortality.11 A study of 1,448 untreated patients with Fabry reported ventricular arrhythmias in 14% and 20% of affected males and females, respectively.11

A proposed Fabry disease cardiac variant has been identified, with a high prevalence in the Taiwanese Chinese population.12 This disease phenotype typically presents in the fifth to eighth decades of life with cardiac involvement, which includes left ventricular hypertrophy, cardiomyopathy, and rhythm abnormalities, in the absence of classical symptoms of Fabry disease.12

A number of “cardiac variant” α-galactosidase A (GLA) gene mutations have been identified, the most common of which is the IVS4+919G>A mutation, which is thought to contribute to approximately 80% of cases.12

Gastrointestinal (GI) Implications

Fabry data shows that 50% of patients reported GI symptoms.4 The most common GI symptoms are abdominal pain, often occurring after eating, and diarrhea.4 Constipation, nausea, and vomiting are other common symptoms.4 The median age of onset for many GI symptoms is before the age of 15 years.4 Data from a Fabry Outcome Survey* reported that 60% of children under age 10 presented with GI symptoms—most frequently reporting altered bowel habits and abdominal pain.4 In another report, only 18% of children were reported to present with gastrointestinal symptoms.4

*Sponsored by Shire.

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  1. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30. doi:10.1186/1750-1172-5-30.
  2. Wijburg FA, Benichou B, Bichet DG, et al. Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial. PLoS One. 2015;10:e0124987.
  3. Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P. Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet Med. 2009;11(11):790-796.
  4. Mehta A, Beck M, Eyskens F, et al. Fabry disease: a review of current management strategies. Q J Med. 2010;103(9):641-659.
  5. Thadhani R, Wolf M, West ML, et al. Patients with Fabry disease on dialysis in the United States. Kidney Int. 2002;61:249-255.
  6. Kampmann C, Perrin A, Beck M. Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: cardiac outcomes after 10 years’ treatment. Orphanet J Rare Dis. 2015;10:125.
  7. Linhart A, Kampmann C, Zamorano JL, et al. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J. 2007;28(10):1228-1235.
  8. Patel MR, Cecchi F, Cizmarik M, et al. Cardiovascular events in patients with Fabry disease: natural history data from the Fabry registry. J Am Coll Cardiol. 2011;57(9):1093-1099.
  9. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet. 2001;38:750-760.
  10. Seydelmann N, Wanner C, Stork S, Ertl G, Weidemann F. Fabry disease and the heart. Best Pract Res Clin Endocrinol Metab. 2015;29(2):195-204.
  11. Acharya D, Robertson P, Kay N, et al. Arrhythmias in Fabry cardiomyopathy. Clin Cardiol. 2012;35:738-740.
  12. Lin HY, Chong KW, Hsu JH, et al. High incidence of the cardiac variant of Fabry disease revealed by newborn screening in the Taiwan Chinese population. Circ Cardiovasc Genet. 2009;2(5):450-456.
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