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.

Pathogenesis:-

• 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.

Histologic Features:-

• 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.

REFERENCES:-

Shafer’s 8th edition