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Fabry disease (FD) is an X-linked hereditary disorder caused by a deficiency of alpha-galactosidase A, leading to intracellular deposition of glycosphingolipids in various tissues and organs.
Report the case of a patient with FD that presents with an atypical manifestation of the disease.
A 58-year old male diagnosed with classical phenotype FD in 2016 was hospitalized because of abdominal pain. He had evidence of neurological, ophthalmological, and cutaneous involvement and markers of advanced disease: hypertrophic-ischemic cardiomyopathy, and stage IIIB-A3 chronic kidney disease. Following the FD diagnosis, enzyme replacement therapy (ERT) with Agalsidase alfa was initiated.
The patient was admitted to the emergency department with diffuse abdominal pain accompanied by non-dysenteric diarrhea. Laboratory findings revealed leukopenia with lymphopenia, ESR 57 mm/h, serum creatinine 2.1 mg/dL, urea 66 mg/dL, K 4.2 mEq/L. Abdominal CT scan showed dilatation of the proximal left colon up to the rectosigmoid junction. Exploratory laparoscopy revealed complicated diverticulitis with perforation of a large diverticulum in the jejunum [Figure 1]. Resection and primary anastomosis were performed.
Following the surgery the patient developed worsening renal failure complicated with hypervolemia unresponsive to diuretic treatment, requiring initiation of hemodialysis (HD).
Histopathological examination with electron microscopy (EM) of the resected intestinal segment showed glycosphingolipid deposits, characterized as "zebra bodies" which are typical of FD [Figure 2A]. These same lesions had been previously demonstrated in the renal biopsy performed in 2016 [Figures 2B and 2C].
Conclusions
Although gastrointestinal involvement is frequent in FD, it is often overlooked due to the nonspecific nature of symptoms, resulting in a delayed diagnosis. Abdominal pain, nausea, vomiting, diarrhea or constipation occur in approximately 20-70% of patients. These symptoms are caused by the deposition of glycosphingolipids in the autonomic intestinal ganglia and mesenteric blood vessels, leading to intestinal dysmotility, autonomic dysfunction, vasculopathy and myopathy.
Small bowel diverticula are typically asymptomatic but can rarely lead to severe and life threatening complications. The location of diverticula has been observed in duodenum, jejunum and colon. The formation of diverticula results from prolonged intestinal dysmotility, causing increased intraluminal pressure and mucosal protrusion.
We present a case of FD diagnosed at an advanced stage, that after 7 years of ERT developed a severe gastrointestinal complication, which precipitated the beginning of HD. We emphasize the presence of considerably large diverticula, promoted by the nature of FD. Supporting this hypothesis, "zebra bodies" were histologically documented in the diverticular lesions. This clinical case demonstrates the importance of a low threshold for the diagnosis of gastrointestinal complications in patients with FD and particularly in this patient the performance of laparoscopy was crucial for the timely diagnosis. This case report stands out for its rarity in revealing zebra bodies in jejunal diverticulum on EM.