title: Gastrointestinal manifestations of Fabry disease: clinical response to enzyme replacement therapy.
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, alpha-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.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine of New York University, New York, NY 1029, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Banikazemi
authors.forename: Thomas
authors.initials: T
authors.lastname: Ullman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D015746:Abdominal Pain / Q000209:etiology / Q000517:prevention & control; D000293:Adolescent; D000328:Adult; D002986:Clinical Trials as Topic; D003967:Diarrhea / Q000209:etiology / Q000517:prevention & control; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy*; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use*; D008297:Male; D011788:Quality of Life; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D000519:alpha-Galactosidase; C459420:agalsidase beta