Gastroenterological Complications of Anderson-Fabry Disease

Abstract

Fabry disease is a multisystemic X-linked lysosomal storage disorder, caused by the partial or complete deficiency of alpha-galactosidase A activity. The storage of glycosphingolipids in the vascular endothelium and in various tissues can lead to a broad spectrum of clinical manifestations. Renal failure, cardiovascular disease, and strokes are the main causes of morbidity and mortality. Gastrointestinal symptoms, although common, are often under-reported in the literature. This review covers the gastroenterological aspects of Fabry disease.

Gastrointestinal involvement in Fabry disease. So important, yet often neglected

“…Patient reports of post-prandial pain, nausea, and vomiting declined steadily with time on treatment, showing statistically significant improvements by week 24. Hoffmann et al, using the Fabry Outcome Survey database, found that the prevalence of gastrointestinal symptoms was reduced following ERT after 12 and 24 months (6). Finally, in four adult patients, after 6-7 months of agalsidase beta therapy, all patients reported 'no or only occasional' abdominal pain or diarrhea and had discontinued their gastrointestinal medications (7).…”

Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

“…A transgenic mouse, which lacks functional α-Gal A enzyme, is available and serves as a model for the human Fabry disease (2). Symptoms of human Fabry disease include severe pain episodes starting in childhood, followed by autonomic and sensory impairment, which reflects damage to small fibers of the peripheral and autonomic nervous systems, kidney failure, and cardiological as well as other symptoms (3–8). Neuropathic pain is the first symptom that arises in many patients and is due to changes in small myelinated and unmyelinated fibers in the periphery (9).…”

“…Differential treatment responses may correlate with genetic variations within the GLA gene where 637 genetic variants including 410 single nucleotide polymorphisms are known to date 1 . Morphological studies report a reduction of small nerve fibers and deficits in ion channel immunoreactivity in Fabry disease patients suggesting a major contribution of defective primary afferent neurons to the Fabry disease small-fiber neuropathy phenotype (3–7, 14). Lysosomal accumulation of Gb3 is characteristic for Fabry disease, and although Gb3 has been found to alter ion channel function (15–17), its relevance for the pathogenesis of heart, kidney, and neurological deficits including pain is yet incompletely understood.…”

Chronic intestinal pseudo-obstruction. Did you search for lysosomal storage diseases?

“…In heterozygous patients (females) almost half of them may experience GI symptoms and some of those symptoms, such as constipation, are reported almost twice as often by female patients as by male patients [11].…”

“…In some patients, colonic dysmotility can lead to the pseudo-obstruction syndrome, simulating intestinal necrosis. That is why up to this date colostomy has been performed in some cases [11], [15], even for children with FD without cardiac, renal or cerebrovascular compromise. Intestinal perforation, secondary to diverticular disease, has been repeatedly described in the literature.…”