By: Dr. Abhishek Kumar Pandey, Asstt. Editor-ICN
LUCKNOW: Our body cells have morphologically diverse sac like structures, Lysosomes. Their primary goals is to breakdown or degrade the proteins, lipids, nucleic acids, carbohydrates, food particles and engulfed bacteria and viruses in the presence of some specific hydrolytic enzymes. Mutation in the genes encoding for these lysosomal hydrolytic enzymes or defects in any non- lysosomal activities involved in lysosomal biogenesis or protein maturation causes lysosomal storage diseases.
Gaucher disease is one of the lysosomal storage disorders and is an autosomal inherited recessive disease. Out of approximately 50 known lysosomal storage diseases, the most common among these inborn errors of metabolism, is Gauchers disease. It is caused due to mutation in the structural enzyme encoding housekeeping gene, GBA1 located on chromosome 21, thus causing a defective or reduced stability and catalytic activity of glucocerebrosidase (enzyme beta-glucosidase).
This disease is the result of a build-up of certain fatty substances in some organs like spleen and liver. This causes these organs to enlarge and can affect their function. The fatty substances can also build up in the bone and increasing the risk of fractures. If the bone marrow is affected, it can interfere with blood’s ability to clot. An enzyme that breaks down these fatty substances doesn’t work properly in peoples with Gaucher disease.
Glucocerebrosidase is a major constituent of red and white blood cells, and the macrophages responsible to remove theses blood cells become unable to eliminate this glycolipid constituent. Therefore it continues to accumulate abnormally throughout the body, especially in the organs like bone marrow, liver, skeleton, lungs and spleen, thus giving rise to characteristic Gaucher cells with a distinctive appearance of “crumpled tissue” and displaced nuclei. These glucosylceramide-laden macrophages or Gaucher cells are the hallmark of Gaucher disease and were first identified by Phillippe Gaucher in 1882 in a splenic aspirate during spleen evaluation studies but was correctly recognised as lysosomal storage disorder by Epstein in 1924. Gaucher’s disease patients are at a high risk of Parkinson’s disease due to defective cellular waste removal and accumulation of dysfunctional mitochondrial cells.
It is basically of 3 types-
1). Non- neuropathic GD1– It is the most commonest form which doesn’t pose any effects on brain and nervous system and can appear at any age. Affected children have stunted growth, delayed puberty and later on suffer from splenomegaly, liver enlargement, anaemia, thrombocytopenia etc.
2). Acute-neuronopathic GD2- A quite rare form of infantile cerebral Gaucher disease and is quite severe as it occurs in the first year of life of a child, making the affected children not live beyond the age of two. Severe manifestations are observed that include rapid progressive neurological problems like gliosis, dry scaly skin (ichthyosis), hydrops fetalis, neuronal loss, neuronophgia, occlumotor dysfunction, seizures etc.
3). Chronic-neuronopathic GD3-This type is also rare. It is characterised by progressive dementia, ataxia, involvement of central nervous system and bones.
The gold standard test for all variants of Gaucher disease is detection of insufficient\reduced beta-glucosidase activity in the affected individual, mostly in the peripheral leukocytes.
Gaucher disease can’t be cured, but its symptoms can be prevented from worsening and patient’s quality of life can be improved by variety of therapies like splenectomy and bone marrow transplantation. For type 1 and type 2 affected, enzyme replacement therapies (ERT) are done. The drawbacks of ERT are its high cost and the immune mediated hypersensitivity. For patients who can’t afford the cost of ERT, substrate reduction therapy is provided which decreases beta glucosidase synthesis. Other medications are prescribed to reduce the hepatic and splenic sizes and increase the platelet count in the affected.
Since it is a genetic defect and can’t be prevented, the foremost requirement for affected individuals is a strong emotional support, positive outlook and social relationships from their close ones. The treatment of any form of Gaucher disease is not quite affordable for a common man even if other treatment modalities are available, as this disease doesn’t manifest with a single symptom but attacks with multi-organ involvement including organomegaly and neurodegeneration.
