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

Abstract

Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A which causes accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Gastrointestinal signs and symptoms-abdominal pain, nausea, diarrhea and diverticular disease--are some of the most frequently reported complaints in patients with Fabry disease but are often neglected. Gastrointestinal symptoms are due to intestinal dysmotility as well as impaired autonomic function, vasculopathy and myopathy. Since 2001, enzyme replacement therapy has been a mainstay in treatment of gastrointestinal symptoms of Fabry disease (FD), resulting in reduced gastrointestinal symptoms. Here, we report on four patients with Fabry disease (FD) who manifested early gastrointestinal involvement.

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

“…In FD, gastrointestinal symptoms occur in approximately 70% of male patients [4], [5], but the frequency ranges from 19% to 69% in different series [9], [10]. 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].…”

“…Substrate deposits of GL-3 in autonomic ganglia (dorsal root ganglia -DRG- and myenteric and submucosal ganglia) may be the cellular alteration which results in the appearance of symptoms [18], [19], [20], [21], [22]. Intestinal ischaemia due myenteric vessel occlusion could also be correlated with the small fiber neuropathy as a result of vasa nervorum obliteration [4]. Animal models with FD showed mechanical hypersensitivity in the von- Frey test and mechanical allodynia when compared with controls [23], [24].…”

“…Furthermore, CIPO often passes unrecognized for long periods of time, so that patients almost invariably undergo repeated, unnecessary and potentially invasive surgical procedures [1]. Fabry disease (FD) is an X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal (GI) involvement such as diarrhea, abdominal pain, early satiety and nausea [4]. The deficiency in lysosomal α-Gal A causes accumulation of globotriaosylceramide (GL-3) within the lysosomes of multiple cell types throughout the body.…”

Effectiveness of enzyme replacement therapy in Fabry disease: Long term experience in Argentina

“…In our study, two patients died due to sepsis. It is important to mention that although sepsis has not been described as a typical complication of FD, it has been associated with intestinal ischemic events and other vascular events in the disease [16].…”

The neurological manifestations of Fabry disease. A review

“…Заместительная терапия эффектив-на при легком и умеренном поражении почек, но неэф-фективна в тяжелых случаях (при протеинурии >1 г/сутки и грубом снижении уровня клубочковой фильтрации) [107][108][109]. При раннем начале лечения отмечается улуч-шение функционирования ЖКТ [110][111][112].…”