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Case Details

A 25 –year-old women presents, with a history that includes-

a) Hepatosplenomegaly with eventual removal of spleen

b) Bone and joint pains with several fractures of femur.

c) A liver biopsy that shows wrinkled looking cells with accumulation of Glucosyl ceramide,

What would be the likely diagnosis for this patient?

Case discussion

The patient is suffering from Gaucher disease. It is an inherited disorder of Cerebroside metabolism.

Basic concept

Cerebrosides occur in large amount in the white matter of brain and in the myelin sheath of nerves. Structurally, Cerebrosides contain a carbohydrate which is generally galactose or sometimes glucose, a high molecular weight fatty acid, an alcohol which is sphingosine or Dihydro sphingosine (See the structure below-figure-1).There is no glycerol, no phosphoric acid and no nitrogenous base. Individual cerebrosides are differentiated by the type of fatty acid present in them.

Figure-1- showing structure of Glucocerebroside(Glucosyl Ceramide). Sphingosine+ Fatty acid(Oleic acid in the given structure) is Ceramide. Ceramide can be further attached with either Glucose or Galactose.

Gaucher disease

This disease is a multisystem lipidosis characterized by hematological changes, organomegaly and skeletal involvement, the latter is usually manifested in the form of bone pains and multiple fractures. It is the most common genetic disorder among Ashkenazi Jews. It is the commonest Lysosomal storage disease.


It is Autosomal recessive in nature.

Biochemical defect

Gaucher’s disease results from deficient activity of Lysosomal Hydrolase, β- Glucocerebrosidase. The enzyme defect results in accumulation of undegraded glycolipid in the form of Glucosyl ceramide in the cells of reticuloendothelial system (figure-2). This progressive accumulation results in infiltration of bone marrow, hepatosplenomegaly and skeletal complications.

Figure-2- showing the formation of Gaucher cell

Clinical features

There are three clinical sub types depending upon the presence of, absence of or progression of neurological complications-

1)Type-1- It accounts for 99 % of cases. The age of onset is variable, from early childhood to late adulthood. The patients present with easy bruising due to thrombocytopenia, chronic fatigue due to anemia, hepatomegaly with or without impaired liver functions. Progressive enlargement of spleen is there which can become massive. Clinical bone involvement is apparent which is manifested in the form of bone pains, or pathological fractures.  The hall-mark of Gaucher’s disease is gaucher cells in the reticuloendothelial system, particularly in the bone marrow. These cells have a typical appearance, they are 20-100μm in diameter, wrinkled looking due to the presence of intracytoplasmic inclusion bodies(figure-2 and 3). The presence of these cells is highly diagnostic of Gaucher’s disease.

Figure3– showing Gaucher cell

2) Type 2 is less common, it is characterized by neurodegeneration, extreme visceral involvement and death within 2 years of life. The death is due to respiratory compromise.

3) Type 3- is intermediate in presentation to type 1 and 2. Neurological involvement is there but occurs later in life with decreased severity as compared to Type 2.

Laboratory Diagnosis

The following studies are indicated in gaucher disease:

  • Enzyme activity testing: Diagnosis can be confirmed  through measurement of Glucocerebrosidase activity in peripheral blood leukocytes. A finding of less than 15% of mean  normal activity is diagnostic.
  • Genotype testing: Molecular diagnosis  can be helpful, especially in Ashkenazi patients, in whom 6 GBA mutations account for most disease alleles.
  • CBC count: Obtain CBC count and differential to assess the degree of cytopenia.
  • Liver function enzyme testing: Minor elevations of liver enzyme levels are common, even in patients who are mildly affected with Gaucher disease; however, the presence of jaundice or impaired hepatocellular synthetic function merits a full hepatic evaluation. 

Imaging Studies

  • Ultrasonography: Ultrasonography of the abdomen can reveal the extent of organomegaly.
  • MRI
    • MRI is more accurate than ultrasonography in determining organ size.
    • Hip MRI may be useful in revealing early avascular necrosis.
    • MRI may be useful in delineating the degree of marrow infiltration and evaluating spinal involvement.
  • Radiography
    • Skeletal radiography can be used to detect and evaluate skeletal manifestations of Gaucher disease.
    • Perform chest radiography to evaluate pulmonary manifestations.
  • Bone marrow examination for the presence of Gaucher’s cells is diagnostic.
  • Liver biopsy – Liver biopsy is occasionally performed to assess unexplained hepatomegaly.


 1) Enzyme replacement therapy (ERT) by recombinant β- Glucocerebrosidase is currently done. This preparation is highly effective in reversing the visceral and hematologic manifestations of gaucher disease. However, skeletal disease is slow to respond, and pulmonary involvement is relatively resistant to the enzyme.

2) Surgical Care

Partial and total Splenectomy was once advocated in the treatment of patients with Gaucher disease. However, with the availability of ERT, this procedure is no longer necessary in most patients.

3) Bone marrow transplant is also helpful.

4) Gene replacement is the permanent cure.


  • Many individuals with Gaucher disease have few manifestations and a normal life expectancy without any intervention.
  • The prognosis for symptomatic patients with type 1 or type 3 Gaucher disease who receive treatment is very good, with a decrease in organomegaly and an eventual rise in hemoglobin levels and platelet counts.
  • Skeletal disease is slow to respond to ERT and widely varies.
  • Some patients describe symptomatic improvement within the first year of treatment, although a much longer period of ERT is required to achieve a radiologic response.
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