|
Indian Pediatr 2011;48: 801-802 |
|
Gaucher’s Disease Presenting with Portal
Hypertension |
Ranjana Bandyopadhyay, *Sanjay Bandyopadhyay and *Pranab
K Maity
From the Department of Pathology, Medical College, 88,
College Street; *Department of Medicine, Nil Ratan Sircar Medical College
& Hospital, 138, A J C Bose Road; Kolkata, India.
Correspondence to: Dr Sanjay Bandyopadhyay, 1B/3,
Uttarpara Housing Estate, 88 B, G T Road, PO Bhadrakali,
Dist Hooghly, 712 232, West Bengal, India.
Email: [email protected]
Received: February 26, 2010;
Initial eeview: May 25, 2010;
Accepted: July 9, 2010.
|
Gaucher’s disease is a rare lysosomal storage disorder characterized by
abnormal accumulation of lipid-laden macrophages in different organs.
Though hepatosplenomegaly is commonly found, symptomatic presentation
with portal hypertension is rare. We report a child with liver cirrhosis
and bleeding esophageal varices who was diagnosed with Gaucher’s disease
disease.
Key words: Gaucher’s disease, Portal hypertension.
|
G aucher’s disease (GD) is an
autosomal
recessive lysosomal storage disorder usually
presenting with hematological or skeletal
manifestations [1]. Symptomatic portal hyper-tension in GD is rare [2,3].
We report two siblings with GD who presented in early childhood with
esophageal variceal bleeding due to accompanying cirrhosis.
Case Report
A three-year-old male child, born to non-consanguinous
parents, presented with insidious onset progressive swelling of abdomen,
early satiety, poor weight gain and generalized weakness for one year.
There was no history of fever, jaundice, bleeding, abdominal pain,
respiratory or urinary symptoms. His birth history and postnatal period
were normal. He had a history of hospital admission for anemia on two
occasions, eight and six months back, and was discharged after blood
transfusion. Patient had two episodes of hematemesis two days back and was
referred to us.
Previous investigations had revealed microcytic
hypochromic anemia, normal liver and renal function tests, and
hepatosplenomegaly on abdominal ultrasound. Bone marrow aspiration was
suggestive of iron-deficiency. His elder brother, four years older to him,
also had similar history and clinical features and died at five years of
age during an episode of variceal bleeding. Complete hematological workup
in that child also did not reveal anything apart from iron deficiency.
On presentation, moderate mental retardation, moderate
pallor, right axillary lymphadenopathy, sternal tenderness, mild
hepatomegaly and huge splenomegaly were present, but no edema, jaundice or
ascites. Neurological examination was normal. Routine investigations were
essentially normal apart from microcytic hypochromic anemia. Grade II
esophagal varices were noted on upper gastrointestinal endoscopy. Apart
from a low albumin (2.6 g/d), liver function test were normal. Doppler
study revealed dilated portal vein with collaterals at the splenic hilum.
Portal venous flow was hepatopetal, and vena cava and hepatic veins were
normal. Liver biopsy showed pericellular and perisinusoidal increased and
thickened reticulin fibers along with portal, periportal and irregular
lobular fibrosis. Features were consistent with cirrhosis. Tests for
hepatitis B, hepatitis C, human immunodeficiency virus, Wilson’s disease,
a-1
antitrypsin deficiency, autoimmune liver disease and cholestatic liver
disease were negative.
Patient was treated with sclerotherapy for variceal
bleeding. Biopsy of the axillary lymph node showed numerous large cells
with abundant pale streaky cytoplasm infiltrating the sinusoids and
suggested the possibility of storage disorder. Bone marrow biopsy revealed
increased reticulin fibers and replacement of hematopoietic elements by
periodic acid Schiff (PAS)-positive large cells having small oval nuclei
with abundant eosinophilic wrinkled cytoplasm suggesting the possibility
of GD. Finally, acid- a
glucosidase activity in peripheral blood lymphocytes was
found to be low (12%; normal greater than 30%). A diag-nosis of GD (type
I) with portal hypertension was made. As his parents could neither afford
the genetic analysis nor enzyme replacement, he is being treated with
transfusion and iron supplement for his anemia, and repeated sessions of
sclerotherapy till the obliteration of varix. Presently, he is under
regular follow up.
Discussion
Many patients with GD have varying degrees of
hepatomegaly, and infiltration of liver with Gaucher’s cells may occur
preferentially after splenectomy. In majority, the liver infiltration is
clinically silent and the serum tests of liver function are generally
normal or only marginally disturbed [4,5]. Hepatic failure and
complications of portal hypertension are rare and their presence suggests
poor prognosis [2,3,5]. Bleeding from esophageal varices has been rarely
noted [6]. Patient affected are usually in first two decades of life and
usually have other florid manifestations of the disease [5-7].
Liver histology in patients with GD with portal
hypertension is characterized by fibrosis [5-7]. The accumulation of
glucocerebroside in the macrophages is undoubtedly the mechanism of
progressive onset of hepatic fibrosis and cirrhosis. Neither viable
Gaucher’s cells nor hepatocytes are seen in the central parts of these
fibrotic zones, which are acellular suggesting that the fibrosis in part
have followed ischemia and infarction [7].
Of the two siblings reported, the first was lost to
follow up before the work up for portal hypertension could be initiated.
The younger one was found to have GD by relevant investigations. However,
his liver biopsy showed features consistent with cirrhosis, but no
Gaucher’s cells. As the etiological workup in this patient could not
identify any other cause of cirrhosis, we conclude that hepatic fibrosis
occurred in response to metabolic insult to the liver.
Contributors: RB: Concept, collection of data,
literature search, SB: conceptualization, preparation of first draft,
intellectual inputs for revision; PKM: literature search. All authors
approved the final draft; SB: shall stand gurantor.
Funding: None.
Competing interests: None stated.
References
1. Elstein D, Abrahamov A, Hadas-Halpern I, Zimran A.
Gaucher’s disease. Lancet. 2001;358:324-7.
2. Charrow J, Andersson HC, Kaplan P, Kolodny EH,
Mistry P, Pastores G, et al. The Gaucher Registry : demographics
and disease characteristics of 1698 patients with Gaucher’s disease. Arch
Intern Med. 2000;160:2835-43.
3. Cano Ruiz A, Martin Scapa A, Menscillo Francia A,
Moreno Caparro’s A. Gaucher’s disease type 1 : an infrequent cause of
portal hypertension. Ann Med Interna. 1998;15:483-4.
4. Zimran A, Kay A, Gelbart T, Garver P, Thurston D,
Saven A, et al. Gaucher disease. Clinical, laboratory, radiologic,
and genetic features of 53 patients. Medicine (Baltimore). 1992;71:337-53.
5. James SP, Stromeyer FW, Chang C, Barranger JA. Liver
abnormalities in patients with Gaucher’s disease. Gastroenterology.
1981;80:126-33.
6. Adrika D, Garfinkel D, Rothem A, Pinkhas J. Fatal
bleeding from esophageal varices in a patient with Gaucher’s disease. Am J
Gastroenterol. 2008;77:838-39.
7. Lachmann RH, Wight DG, Lomas DJ, Fisher NC,
Schofield JP, Elias E, et al. Massive hepatic fibrosis in Gaucher’s
disease: clinico-pathological and radiological features. QJM.
2000;93:4237-44.
8. Harmanci O, Bayraktar Y. Gaucher disease: New
developments in treatment and etiology. World J Gastroenterol.
2008;14:3968-73.
9. Beutler E. Lysosomal storage diseases: natural
history and ethical and economic aspects. Mol Genet Metab. 2006;88:208-15.
10. Taddei T, Mistry P, Schilsky ML. Inherited metabolic disease of the
liver. Curr Opin Gastroenterol. 2008;24: 278-86.
|
|
|
|