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Gaucher's Disease: A Case Report

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Dr Preeti Bajaj, Dept. of Pathology, Dr Vasantrao Pawar Medical College, Hospital & Research Centre, Nashik - 422013    23 September 2021

Abstract

Gaucher’s disease (GD) is an autosomal recessive systemic lysosomal storage disorder which is characterized by glucocerebroside deposition in cells of the macrophage-monocyte system as a result of a deficiency in lysosomal β-glucosidase (glucocerebrosidase). GD is a rare genetic disorder. It is the most common amongst the lysosomal storage disorders. GD has been categorized into three types based on the presence of central nervous involvement.1 Type 1 is a non-neuronopathic form that presents in childhood or early adulthood. Type 2 is acute neuronopathic form that presents in childhood. It progresses rapidly and is fatal. Type 3 is chronic non-neuronopathic form that presents in childhood but is slowly progressive. Here we describe a case of a 3½ - year-old male child in whom a diagnosis of GD was made based on bone marrow biopsy and later confirmed by glucocerebrosidase levels estimation.2

Gaucher’s disease (GD), a lysosomal storage disorder is caused by a defect in the housekeeping gene lysosomal glucocerebrosidase which is present on the first chromosome (1q22).3 It was first described by a French physician, Philippe Charles Ernest Gaucher in a 32-year-old woman whose liver and spleen were enlarged. The incidence of GD worldwide is approximately 1/57,000 to 1/75,000 births. In Ashkenazi Jews, the incidence is 1/800 births. 

In India, GD is believed to be extremely rare and has been reported only in a few case reports.4 Out of the three types of GD, type 1 is the most common type, which represents 95% of all cases. It is generally characterized by hepatosplenomegaly, bone and lung disease, hematologic abnormalities such as anemia, thrombocytopenia and coagulation abnormalities. Central nervous system is not involved. It occurs most commonly among Ashkenazi Jews. Type 2 has a severe progression with onset prior to 2 years, with neurologic disease, hepatosplenomegaly and lung disease. Death usually occurs between 2 and 4 years of age due to lung failure. Patients with type 3 may have onset prior to 2 years of age, but the progression is not as severe. These individuals may survive into the third and fourth decade. Apart from this, a perinatal lethal and a cardiovascular form of GD also exist. 

Case Presentation

A 3½-year-old male child, Hindu by religion, born to parents of nonconsanguineous marriage was admitted to a tertiary care hospital with predominant clinical presentation of bicytopenia and hepatosplenomegaly. The child had delayed milestones. On examination, the child was pale. Liver was 5 cm palpable below the right costochondral margin. The spleen was 10 cm palpable below the left costochondral margin. Peripheral blood smear examination revealed bicytopenia. Hemoglobin was 7.2g/dL and platelet count was 70,000/µL. Bone marrow biopsy was done. Bone marrow biopsy showed sheets of Gaucher cells (Figs. 1 and 2) seen as histiocyes with abundant granular and fibrillar cytoplasm. These cells had small eccentrically placed nuclei were noted. The gaucher cells had a crumpled tissue paper appearance. The diagnosis of GD was given on bone marrow biopsy. Enzyme β-glucocerebrosidase levels were outsourced. β-glucocerebrosidase levels in peripheral leukocytes were reported to be 0.31 nmol/h/mg protein. Values < 8.7 nmol/h/mg protein are consistent with a diagnosis of GD.

Discussion 

GD is usually diagnosed by the demonstration of characteristic “Gaucher cells” in the bone marrow. Pseudo-Gaucher cells have occasionally been described in various hematologic malignancies including multiple myeloma, myelodysplastic syndrome, lymphomas, chronic myelogenous leukemia and thalassemia.5 Therefore, detection of reduced or absent β-glucosidase (glucocerebrosidase) enzyme activity is the gold standard for the diagnosis of all the variants of GD.1

Absent or reduced activity of this enzyme results in accumulation of undigested materials (primarily in the lysosomes) and interferes with the normal functioning of cells. The excess accumulation of the glucocerebroside (glucosylceramide) in the macrophages is the main manifestation in the various visceral organs.6 GD has a varied and multiorgan presentation. Diagnosing GD may pose a challenge.7 Serum β-glucosidase levels < 15% of mean normal activity confirms the diagnosis.2 

Treatment is available in the form of enzyme replacement therapy. For types 1 and 3, substrate inhibition therapy represents a viable alternate approach to enzyme therapy in the treatment of visceral pathology in GD.8 Bone marrow transplantation may benefit type 3 individuals. Currently, only supportive therapy is available for type 2. Differential diagnosis of GD must be kept while dealing with patients having massive hepatosplenomegaly.9

References

  1. Bohra V, Nair V. Gaucher’s disease. Indian J Endocrinol Metab. 2011;15(3):182-6.
  2. Patel AL1, Shaikh WA, Khobragade AK, Soni HG, Joshi AS, Sahasrabudhe GS, et al. Gaucher’s disease. J Assoc Physicians India. 2009;57:410-1.
  3. Ahmadieh A, Farnad F, Sedghizadeh PP. Gaucher disease with jawbone involvement: a case report. J Med Case Rep. 2014;8:360.  
  4. Nagral A, Mewawalla P, Jagadeesh S, Kabra M, Phadke SR, Verma IC, et al. Recombinant macrophage targeted enzyme replacement therapy for Gaucher disease in India. Indian Pediatr. 2011;48(10):779-84.
  5. Ash Image Bank. Waldenström macroglobulinemia with pseudo-Gaucher cells. Blood. 2010;116(18):3388.
  6. Beutler E, Grabowski GA. Glucosylceramide lipidosis-Gaucher disease. The metabolic and molecular bases of inherited diseases. 8th ed. New York: Mc Graw –Hill; 2001. p. 3635-68.
  7. Neelaveni N, Anunayi J, Raju YR, et al. Pediatric Non-neuronopathic Gaucher disease- a case report. Sch J Med Case Rep. 2014;2(2):96-9.
  8. McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang WL, Hutto E, et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007;91(3):259-67.
  9. Priyani AAH. Gaucher’s disease: a rare disease with an unusual presentation. Journal of Diagnostic Pathology. 2014;9(1):33-6.

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