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.