Gastrointestinal symptoms in 342 patients with Fabry disease: prevalence and response to enzyme replacement therapy.

BACKGROUND & AIMS: Fabry disease is an X-linked deficiency of alpha-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.

Nature and prevalence of pain in Fabry disease and its response to enzyme replacement therapy--a retrospective analysis from the Fabry Outcome Survey.

BACKGROUND: Fabry disease is a multisystemic life-threatening lysosomal storage disorder caused by deficiency of alpha-galactosidase A. Symptoms of the disease may occur in different organs including kidney, heart, and the nervous system. OBJECTIVES: To evaluate the nature and prevalence of pain in a large cohort of patients with Fabry disease and to assess the effect of enzyme replacement therapy (ERT) with agalsidase alfa. METHODS: Retrospective analysis of the data of 752 patients with Fabry disease (393 females, 353 males) enrolled in the Fabry Outcome Survey, a multicentre database. RESULTS: The prevalence of pain in male patients was 81.4% (females 65.3%). Mean age at onset of pain was 14.8+/-1.0 year in males (females 19.8+/-1.4 y). Pain was most frequently reported in the hands (males 76%, females 60%) and feet (males 73%, females 52%), but often affected the whole body. Interference of pain with daily life was higher in females than in males, and was observed predominantly for general activities, mood, and normal work. Fifty-eight percent of the patients were on ERT with agalsidase alfa. At 24 and 36 months after commencement of ERT, pain severity classification shifted towards lower severity (P<0.05). Moreover, after 36 months, "average pain" and "pain now" were significantly reduced (P<0.05). CONCLUSIONS: Pain is one of the most prevalent symptoms in Fabry disease with onset early in childhood. ERT with agalsidase alfa significantly reduces pain in this debilitating disorder.