Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry

Deya Alkhatib; Jesus Avila Vega; Issa Pour-Ghaz; Omar Al-Taweel; Sania Khan; Kimberly DeCarr; Anandbir Bath; Aranyak Rawal; David Wilbanks; Joel Raja; Asra Butt; Neeraja Yedlapati; Robert J Hopkin; John L Jefferies

doi:10.1016/j.ymgme.2023.107538

Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry

Mol Genet Metab. 2023 Apr;138(4):107538. doi: 10.1016/j.ymgme.2023.107538. Epub 2023 Feb 8.

Authors

Affiliations

¹ Division of Cardiovascular Disease, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: dalkhati@uthsc.edu.
² Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
³ Division of Cardiovascular Disease, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
⁴ Cardiology, Las Vegas School of Medicine, University of Nevada, Las Vegas, NV 89154, USA.
⁵ The University of Tennessee Health Science Center - College of Medicine, Memphis, TN 38163, USA.
⁶ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.

PMID: 36812723
DOI: 10.1016/j.ymgme.2023.107538

Abstract

Background: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement. Lymphedema is caused by sphingolipid deposition within lymphatics. Lymphedema can cause intolerable pain and limit daily activities. Very limited data exist on lymphedema in AFD patients.

Methods: Using data from the Fabry Registry (NCT00196742) with 7671 patients included (44% males and 56% females), we analyzed the prevalence of lymphedema among AFD patients who were ever assessed for lymphedema and studied the age of first reported lymphedema. Additionally, we assessed whether patients received AFD-specific treatment at some point during their clinical course. The data was stratified by gender and phenotype.

Results: Our study showed that lymphedema occurred in 16.5% of the Fabry Registry patients who were ever assessed for lymphedema (n = 5487). Male patients when compared to female patient have higher prevalence (21.7% vs 12.7%) and experienced lymphedema at a younger age (median age at first reported lymphedema of 43.7 vs 51.7 years). When compared to other phenotypes, classic phenotype has the highest prevalence of lymphedema with the earliest reported lymphedema. Among those who reported lymphedema, 84.5% received AFD-specific treatment during their clinical course.

Conclusions: Lymphedema is a common manifestation of AFD in both genders, with a tendency to present later in female patients. Recognition of lymphedema can offer an important opportunity for intervention and potential impact on associated morbidity. Additional future studies are needed to characterize the clinical implications of lymphedema in AFD patients and identify additional treatment options for this growing population.

Keywords: AFD; Anderson-Fabry disease; Fabry disease; Genetic disease; Lymphedema; Lymphedema in AFD; Skin manifestation.

MeSH terms

Disease Progression
Fabry Disease* / complications
Fabry Disease* / epidemiology
Fabry Disease* / genetics
Female
Humans
Lymphedema* / etiology
Lymphedema* / genetics
Male
Prevalence
Registries
alpha-Galactosidase / genetics

Substances

alpha-Galactosidase