Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotype.

Abstract

BACKGROUND:

Fabry disease is an inherited disorder of glycolipid metabolism with progressive involvement of multiple organs, including the gastrointestinal tract, in classically affected male patients. Clinical presentations in males with later-onset Fabry phenotypes are more heterogeneous and largely dependent on the level of residual α-galactosidase A activity.

METHODS:

We assessed agalsidase beta treatment outcomes of gastrointestinal symptoms in adult males with classic or later-onset Fabry disease. Self-reports of abdominal pain and diarrhea ('present'/'not present' since previous assessment) at last clinical visit (≥0.5 year of follow-up) were compared with treatment-baseline.

RESULTS:

Classic male patients were considerably younger at first treatment than the fewer males with later-onset phenotypes (36 vs. ~47 years) and reported gastrointestinal symptoms more frequently at baseline (abdominal pain: 56% vs. 13%; diarrhea: 57% vs. 23%). As compared with baseline, significantly fewer classic patients reported abdominal pain after a median of 4.7 years of treatment (N = 171, 56% vs. 41%, P < 0.001). Moreover, significantly fewer patients reported diarrhea after 5.5 years of follow-up (N = 169, 57% vs. 47%, P < 0.05). Among the males with later-onset phenotypes, albeit statistically non-significant, abdominal pain reports reduced after a median of 4.2 years (N = 48, 13% vs. 4%) and diarrhea reports reduced after a median of 4.4 years of treatment (N = 47, 23% vs. 13%).

CONCLUSIONS:

Sustained treatment with agalsidase beta was associated with improvement in abdominal pain and diarrhea in a significant proportion of classic male Fabry patients. Males with later-onset phenotypes reported gastrointestinal symptoms much less frequently at baseline as compared with classic patients, and non-significant reductions were observed.

• Authors: Robert J Hopkin, Ulla Feldt-Rasmussen, Dominique P Germain, Ana Jovanovic, Ana Maria Martins, Kathleen Nicholls, Alberto Ortiz, Juan Politei, Elvira Ponce, Carmen Varas, Frank Weidemann, Meng Yang, William R Wilcox
• Journal: Molecular genetics and metabolism reports (Mol Genet Metab Rep) Vol. 25 Pg. 100670 (Dec 2020) ISSN: 2214-4269 [Print] United States
• PMID: 33163363 (Publication Type: Journal Article)
• Copyright: © 2020 Published by Elsevier Inc.