Gaucher disease (GD) is the commonest lysosomal storage disorder (LSD) with an estimated global incidence of 1: 40,000 to 1:60,000 live births. In the Ashkenazi (Eastern European) Jewish population, with a carrier frequency of 6% compared to 0.7% to 0.8% of the non-Jewish population. Gaucher disease's exact prevalence in India is not fully documented due to a lack of centralized registries, due to the tradition of consanguineous marriages in parts of the country, it seems likely that the frequency of Gaucher disease may be higher in India. The most common form of Gaucher disease is type 1, which has a very variable phenotype ranging from early childhood symptoms to no symptoms throughout life but typically does not have a neurological component. In contrast to type 1, types 2 and 3 are rare and affect the central nervous system.

Glucosylceramide, the accumulated glycolipid, is primarily derived from the phagocytosis and degradation of senescent leukocytes and erythrocyte membranes. The glycolipid storage gives rise to the characteristic Gaucher cells, macrophages engorged with lipid with a crumpled–tissue-paper appearance and displaced nuclei. The factors that contribute to neurologic involvement in patients with types 2 and 3 disease are still unknown but may be related to the accumulation of a cytotoxic glycolipid, glucosylsphingosine, in the brain due to the severe deficiency of glucocerebrosidase activity or to neuroinflammation. Glucosylceramide accumulation in the bone marrow, liver, spleen, lungs, and other organs contributes to pancytopenia, massive hepatosplenomegaly, and, at times, diffuse infiltrative pulmonary disease. Progressive infiltration of Gaucher cells in the bone marrow may lead to thinning of the cortex, pathologic fractures, bone pain, bony infarcts, and osteopenia.

Individuals with Gaucher disease may exhibit the following signs and symptoms:

Enlargement of the spleen (splenomegaly)

• Often one of the earliest signs occurring in childhood or adolescence. An enlarged spleen can lead to hypersplenism, where the spleen destroys blood cells, worsening anemia, thrombocytopenia and leukopenia.
• Splenic Infarcts though rare, may occur and cause abdominal pain and digestive issues.

Enlargement of the liver (hepatomegaly)

• May manifest in childhood or adolescence accompanying an enlarged spleen, and may result in liver dysfunction, though it is less common than splenomegaly

Bone Abnormalities

• Includes bone pain, fractures and skeletal abnormalities, which can occur at any age. Individuals with Gaucher disease who experience symptoms in childhood may develop widening of the long bones, known as ‘Erlenmeyer flask deformities.’ Others may develop abnormal bone density or other skeletal changes later in life which can lead to bone fragility and fractures.
• Episodes of severe bone pain called “bone crises” due to infarctions or the death of bone tissue may occur.
• Osteonecrosis is the most severe bone complication, which can lead to significant bone deformities, often requiring pain management and/or surgery.

Hematological abnormalities

• Anemia and thrombocytopenia can occur at various stages and may worsen over time.
  Anemia or low red blood cell count can lead to fatigue and weakness.
• Low platelet counts can increase the risk of bruising and bleeding.

Neurological complications (in GD2 and GD3)

• Includes swallowing difficulties, seizures, muscle stiffness, coordination problems and developmental delay, typically appearing in infancy or childhood. The most common indicator of brain involvement in GD is abnormally slowed eye movements or inability to move the eyes horizontally

The diagnosis of Gaucher disease depends upon finding a low GBA1 enzyme level in peripheral blood leukocytes and establishing the presence of mutant alleles in the GBA1 gene. Even though only a blood sample is needed to diagnose Gaucher disease, some patients undergo unnecessary invasive bone marrow or liver biopsy before making a correct diagnosis

• Laboratory Studies: CBC Count, Liver Function Enzyme Testing and Coagulation
• Enzyme Activity : Diagnosis is confirmed through measurement of glucocerebrosidase activity in peripheral blood leukocytes. Less than 15% of mean normal activity is diagnostic for Gaucher disease
• Genotype Testing: In some ethnicities, sequencing of the exons of GBA1 may be necessary to establish the genotype
• Imaging
• Ultrasonography may reveal abdominal organomegaly
• MRI may be useful in revealing early skeletal involvement (avascular necrosis, spinal degradation, and degree of bone marrow infiltration).
• Radiography may reveal skeletal manifestations and pulmonary involvement.

Bone Marrow Aspiration

• In the past, the diagnosis was made by finding classic glycolipid-laden macrophages in bone marrow aspirate

Liver Biopsy

• A liver biopsy may be performed to evaluate unexplained hepatomegaly