Introduction

 

Gaucher’s disease is the most common lysosomal storage disease, where accumulation of monocytes/macrophages laden with glucosylceramide in liver and spleen leads to hepatosplenomegaly, and rarely to portal hypertension. High threshold of suspicion should  be kept for considering Gaucher’s disease as a diagnostic possibility in patients who present with portal hypertension with hepatosplenomegaly.

 

Case Report

 

A 25 year old female, presented with chief complaints of a progressively increasing lump in left upper abdomen present since age of 8 years. It was associated with easy fatigability. There was no history of easy bruising or prolonged bleeding on trauma, hematemesis, fever, night sweats, weight loss or bone pains. She lived a healthy life with no addictions and normal menstrual cycles. Her family members including her parents, a male child of three years of age and four siblings who were normal and there was no consanguinity among parents. On examination, pallor was noted; however there was no icterus or lymphadenopathy. She had firm, non tender massive splenomegaly and a non tender, firm mild hepatomegaly. Rest of systemic examination was essentially normal.

 

Lab investigations revealed pancytopenia [Hb- 7.0 mg%; TLC- 2,440/ml; DLC- P70/L30; platelet Count- 81,000/ml]. Liver function test, serum proteins and albumin, prothrombin test, kidney function test, urine analysis, 24 hour urinary copper were normal. Antigen test for malaria and leishmania, Mantoux, viral markers, ANA, anti- LKM and HIV were negative. Ultrasound revealed grossly enlarged spleen (22 cm) and splenic vein (16 mm) with mild ascites. Liver span was 13 cm with mildly coarsened echotexture. Portal vein was dilated with diameter of 20 mm with hepatopedal flow. Upper gastrointestinal endoscopy showed grade IV varices with congestive gastropathy. Liver biopsy revealed mild hepatitis with mild portal fibrosis. To evaluate massive splenomegaly in presence of only mild portal fibrosis, bone marrow aspiration with biopsy was done which revealed Gaucher cells in a background of normal erythroid, myeloid and megakaryocytic lineage cells (Figure 1). Confirmation of diagnosis of Gaucher’s disease was done by b glucosidase levels- 3.587 nmol/hv/mg (normal levels >6.0). Pulmonary function test and skeletal survey were normal.

 

Splenectomy with lieno-renal shunt was done for hypersplenism and on histopathology large number of Gaucher cells were seen (Figure 2). Patient was also started on enzyme replacement.

 

Discussion

 

Gaucher’s disease is an autosomal genetic disorder that affects fewer than 10,000 people worldwide. Gaucher’s affects all racial and ethnic groups; prevalence is higher among Ashkenazi Jews. It is the most common lysosomal storage disorder. The genetic defect lies on chromosome 1 thereby resulting in insufficient or ineffective enzyme, glucocerebrosidase. The resultant accumulation of glucosylceramide within cells of monocyte/macrophage origin leads to the visceral manifestations of the disease. Of the three forms, type-1 Gaucher’s is the non neuronic form and also the most common one.

 

Hepatosplenomegaly is a common manifestation of Gaucher’s disease, but portal hypertension is rarely seen. There have been only a few patients with Gaucher’s disease who have been reported in the literature as having portal hypertension.[1,2,3,4,5,6,7,8,9,10] The portal hypertension in Gaucher’s disease can be due to two main factors.[11] First due to increased forward portal blood flow consequent to splenic enlargement; and second due to intrahepatic obstruction from extensive deposits of Gaucher cells, or probably in some cases to a combination of these factors.[11] In our case, the patient presented with hepatosplenomegaly with portal hypertension. The presence of typical Gaucher cells in bone marrow together with decreased enzyme levels confirmed the diagnosis. Apart from portal hypertension there was no other feature of liver involvement in this case and even on liver biopsy, only mild fibrosis was found. Thus, liver disease is unlikely to contribute towards portal hypertension in our case. Hence, forward flow due to splenomegaly seems to be the likely etiology of portal hypertension.

 

Portal hypertension due to splenomegaly can be managed by splenectomy. But portal hypertension due to intrahepatic obstruction is usually irreversible. Without specific treatment the liver disease is progressive and rapidly fatal. However, institution of enzyme replacement therapy with imiglucerase may have beneficial effects even when the condition is far advanced.[1]

 

This case emphasizes the significance of considering Gaucher’s disease as a cause of portal hypertension particularly in patients presenting with hepatosplenomegaly.

 

References

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3.     Choulot JJ, Bargiarelli M, Saint-Martin J. [Portal hypertension complicating Gaucher’s disease (author’s transl)]. Arch Fr Pediatr. 1981;38:267–8.

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10.   Mazor M, Wiznitzer A, Pinku A, Katz M, Leiberman JR. Gaucher’s disease in pregnancy associated with portal hypertension. Am J Obstet Gynecol. 1986;154:1119–20.

11.   Sales JE, Hunt AH. Gaucher’s disease and portal hypertension. Br J Surg. 1970;57:225–8.