Original article—alimentary tract
Gastrointestinal Symptoms in 342 Patients With Fabry Disease: Prevalence and Response to Enzyme Replacement Therapy

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Background & Aims: Fabry disease is an X-linked deficiency of α-galactosidase A, resulting in lysosomal deposition of globotriaosylceramide in nearly all tissues. The disease frequently causes diarrhea and abdominal pain, which are assumed to arise from malfunction of enteric neurons and which mimic diarrhea-predominant irritable bowel syndrome (IBS). There are limited data about the prevalence and nature of gastrointestinal symptoms in patients with Fabry disease and the response to enzyme replacement therapy (ERT) in large cohorts. The aims of this study were to evaluate the nature and prevalence of gastrointestinal symptoms and their impact on health-related quality of life (HRQoL) in patients with Fabry disease and to analyze changes after 12 and 24 months of treatment with agalsidase alfa. Methods: Information about gastrointestinal symptoms was obtained from regular interviews before and during the time of ERT. Data on HRQoL were collected by using the EQ-5D questionnaire. Results: The overall prevalence of gastrointestinal symptoms was 52%, with abdominal pain and diarrhea being most frequent. Female patients were more frequently affected than male patients, and there was a high prevalence in children (abdominal pain, 49.3%; diarrhea 25.4%). ERT with agalsidase alfa reduced the prevalence of abdominal pain, with a statistically significant decrease in male patients and in children after 12 months of treatment. Conclusions: The gastrointestinal symptomatology of Fabry disease is very similar to diarrhea-predominant IBS; however, pathophysiologic similarities remain to be elucidated. ERT reduced the prevalence of gastrointestinal symptoms in Fabry disease, particularly in children and male patients.

Section snippets

Patients and Data Collection

FOS is an open international database for patients with a confirmed diagnosis of Fabry disease. The properties and management of the database have been described previously.3 Briefly, patients are evaluated on symptoms of 16 different organ systems by simple questions during regular visits at their treatment centers. Questions on gastrointestinal symptoms include the manifestation of abdominal pain (its nature, frequency, precipitants) as well as the occurrence of nausea, constipation,

Results

At the time of this analysis (October 2005), 752 patients had been enrolled in the FOS database from 11 countries in Europe. Clinical data on signs and symptoms of Fabry disease were available in 714 individuals (369 female and 345 male) including 127 children younger than the age of 18 years (70 girls, 57 boys). Patient characteristics are summarized in Table 1. Of these, 342 patients had documented information about gastrointestinal symptoms and had not been treated with ERT before or at the

Discussion

Fabry disease is a rare multisystemic inherited metabolic disease with profound effects in almost all organ systems, reduced life expectancy,4 and substantial involvement of the gastrointestinal tract.11, 18, 19, 20, 21, 22, 23, 24, 25 However, most reports are based on single cases or small cohorts. A larger cohort of patients was described by MacDermot et al,4 who reported a prevalence of approximately 70% for gastrointestinal symptoms in 98 male patients with Fabry disease. In this report,

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    See list of Fabry Outcome Survey European Investigators in Appendix 1.

    Data collection and analysis in FOS are supported by Shire Human Genetic Therapies AB (Danderyd, Sweden).

    All authors have received travel grants from Shire Human Genetic Therapies (Shire HGT). B.H., A.M., and S.K. have received honoraria from Shire HGT for giving presentations at medical and scientific meetings. A.M. has received research funding support from Shire HGT.

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