Gastrointestinal manifestations of Fabry disease: Clinical response to enzyme replacement therapy

Maryam Banikazemi, Thomas Ullman, Robert J. Desnick

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Gastrointestinal symptoms are often an early and prominent manifestation of Fabry disease, an X-linked inborn error of metabolism caused by the deficient activity of the lysosomal enzyme, α-galactosidase A. This enzyme deficiency results in the progressive accumulation of globotriaosylceramide and other glycosphingolipids in tissue lysosomes throughout the body. In classically affected patients, glycosphingolipid accumulation in the vascular endothelium eventually culminates in life-threatening renal, cardiac, and cerebrovascular disease. In addition, over 50% of patients experience post-prandial abdominal pain and diarrhea that interferes with the ability to work and quality of life. Here, we describe four males aged 17-40 years with classic Fabry disease and severe gastrointestinal symptoms who participated in clinical trials of enzyme replacement therapy with agalsidase beta (Fabrazyme, 1 mg/kg every 2 weeks). Before therapy, the three adult patients experienced post-prandial abdominal pain, bloating, and severe diarrhea with 7-10 bowel movements per day every day and the 17-year-old had weekly episodes of diarrhea with six bowel movements per day. Other symptoms included vomiting, food intolerance, and poor weight gain. All patients took medications for these symptoms (diphenoxylate-atropine [Lomotil], ranitidine hydrochloride [Zantac], or sulfasalazine). After 6-7 months of agalsidase beta therapy, all patients reported "no or only occasional" abdominal pain or diarrhea, had discontinued their gastrointestinal medications, and had gained 3-8 kg. These marked improvements in gastrointestinal symptoms have persisted for over 3 years of treatment. In such patients, enzyme replacement at 1 mg/kg effects an early and significant clinical improvement in the gastrointestinal manifestations of Fabry disease.

Original languageEnglish (US)
Pages (from-to)255-259
Number of pages5
JournalMolecular Genetics and Metabolism
Volume85
Issue number4
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Keywords

  • Enzyme replacement therapy
  • Fabry disease
  • Gastrointestinal symptoms

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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