Common LSD, characterized by deposition of gluco – cerebroside in cells of macrophage – monocyte system.
Results from mutation in gene or deficiency of enzyme that codes for glucosylceramidase.
Leads to accumulation of glucosylceramide in mononuclear phagocytic cells; transformed into “Gaucher cells“.
Five autosomal recessive variants exist resulting from distinct allelic mutations.
Three have been described in the literature.
- Normally glycolipids derived from breakdown of senescent blood cells are sequentially degraded.
- In this condition, degradation stops at level of glucosylceramidases.
These transit through blood as macromolecules; engulfed by phagocytic cells of the body.
- These phagocytes “Gaucher cells” become enlarged due to accumulation of distended lysosomes
Type I – Chronic nonneuronopathic form:-
- Presents in childhood with hepatosplenomegaly, pancytopenia & skeletal disease.
- Most common variety, striking predilection for Ashkenazi Jews.
Characterized by clinical or radiologic bone involvement.
Spleen enlarges massively filling the entire abdomen.
Type II – Infantile/acute neuronopathic form:-
Rapidly progressive neurovisceral involvement.
Symptoms start before 2 years of age, very severe.
Results in death in infancy.
Type III – Juvenile/ Norrbotnian form:-
Patients are juvenile presenting with systemic involvement.
(intermediate between type I and type II).
Progressive CNS involvement usually begins in teens or early twenties.
- Numerous large, foamy, slightly granular cells with small, round, pyknotic nuclei – replace normal marrow structure.
- Sternal puncture or biopsies of liver or spleen will reveal typical “Gaucher’s cell”.
- Round, pale cell, 20 – 80µ, containing small eccentric nucleus & wrinkled or “crumpled silk” cytoplasm.
Treatment & Prognosis:-
Prognosis of Type II is very poor; death within first year.
Less virulent form may persist till 6th decade.
Administration of purified glucocerebrosidase results in dramatic decrease in hepatic accumulations of glucocerebroside.
Enzyme replacement therapy available; effective but extremely expensive.
Shafer’s 8th edition