A Case of Adult Type 1 Gaucher Disease Complicated by Temporal Intestinal Hemorrhage
A 21-year-old male patient suffering from sudden rectal hemorrhage was admitted to a general hospital in July 2009. Emergent colonoscopy was performed with the findings of (1) a large amount of blood in the rectum and sigmoid colon and (2) oozing from eroded rectal mucosa. Laboratory investigation revealed thrombocytopenia (platelets 10.3 × 104/\nμl). Although the hemorrhage stopped spontaneously and did not occur again, the patient was referred to our hospital for further examinations. He had had no previous significant rectal bleeding. His past medical history was unremarkable except for occasional nasal bleeding during childhood.\nOn physical examination, the abdomen was soft and flat; a non-tender liver edge descended to 8.5 cm below the right costal margin, and the splenic tip was palpable 11.5 cm below the left costal margin. Neurologic examination revealed no evidence of abnormalities. The laboratory data are summarized in table . There were thrombocytopenia and slight leukocytopenia (platelets 6.7 × 104/μl, white blood cells 3,180/μl). Other laboratory findings disclosed: total bilirubin 1.4 mg/dl (reference range 0.2–1.3), direct bilirubin 0.5 mg/dl (reference range 0–0.3), and prothrombin time activity 77.0% (reference range 90–130). To find out the cause of thrombocytopenia and leukocytopenia, we performed serology tests for infection with hepatitis B virus, hepatitis C virus, Epstein-Barr virus and Helicobacter pylori; however, there were no remarkable findings. Anti-DNA antibody test showed a titer of 1:40 (reference range <1:40). His platelet-associated immunoglobulin G (PAIgG) level was elevated to 166 ng/107 cells (reference range 9.0–25.0), however anti-platelet antibody (anti-platelet-binding IgG) was negative.\nEnhanced computed tomography (CT) showed the extremely enlarged liver and spleen. The splenic and the superior mesenteric vein were dilated and tortuous, whereas no apparent cirrhotic change of the liver was observed (fig. ). For further examination, especially for the differential diagnosis of idiopathic portal hypertension, we performed a liver biopsy. The liver biopsy specimen showed that numerous large cells with striated cytoplasm assembled in Glisson's capsule (fig. ). The cells had abundant eosinophilic cytoplasm with a striated or fibrillar appearance like that of crumpled tissue paper, which is typical of Gaucher cells []. There was fibrous expansion of most portal tract areas, but bridging fibrosis was not seen. Additional blood investigations revealed high values of acid phosphatase and angiotensin-converting enzyme (ACE) concentrations (table ), which is compatible with Gaucher disease []. The enzymatic activity of leukocyte β-glucosidase, the measurement of which is necessary for the definitive diagnosis of Gaucher disease, had decreased to 11.67 nmol/h/mg (reference range 56.76–74.85) [, ]. We analyzed the seven common mutations (N370S, 84GG, F213I, IVS2+1, L444P, R463C and D409H) in the GBA gene as previously reported [, , ] with the informed consent of the patient and found the compound heterozygous mutations L444P/D409H. Based on these results, we diagnosed the patient with Gaucher disease type 1.\nWe started enzyme replacement therapy (ERT). 60 U/kg body weight imiglucerase, a macrophage-targeted recombinant human glucocerebrosidase, was injected every 2 weeks []. Figure shows the CT scan 5 months after ERT started. The liver and the spleen were sized down (liver: from 23.3 × 15.4 × 20.3 cm to 22.1 × 15.3 × 17.9 cm; spleen: from 12.8 × 10.5 × 21.1 cm to 11.8 × 9.4 × 17.3 cm). Platelet counts number and ACE concentration, a biomarker of the progress of Gaucher disease [], were also improved from 7.4 to 11.3 × 104/μl and from 42.5 to 24.7 IU/μl, respectively (fig. ).