Gaucher disease

Introduction

Gaucher disease is the most common genetic lysosomal storage disorder^[1] and represents a potentially serious health problem^[2]. In Gaucher disease, a deficiency of the enzyme glucocerebrosidase leads to the accumulation of the lipid glucocerebroside within the lysosomes of the monocyte-macrophage system^[1] As an inborn condition, Gaucher disease has a lifelong duration. Genetic and especially clinical heterogeneity is its hallmark. Gaucher disease frequently follows a progressive, symptomatic course, often with unpredictable and dramatic turns for the worse. Symptoms are usually multisystemic, often debilitating or disabling, sometimes disfiguring, and can lead to death. Indeed, if untreated, the disease may progress and result in pathological features which may become difficult or impossible to reverse (e.g., spleen or liver fibrosis, osteonecrosis)^[3,4]

Lipid-engorged cells with eccentric nuclei, known as Gaucher cells, accumulate and displace healthy normal cells in bone marrow and visceral organs, causing a host of signs, including skeletal deterioration, anemia, hepatosplenomegaly, and organ dysfunction. In rare cases Gaucher cells affect the brain and nervous system^[5]

Images of Gaucher cell (top) and a normal cell (bottom)

References

1. Charrow J, Andersson HC, Kaplan P, et al. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med. 2000;160:2835-2843

2. NIH Technology Assessment Panel on Gaucher Disease. Gaucher disease: current issues in diagnosis and treatment. JAMA. 1996;275:548-553.

3. Barton NW, Rosenthal DI, Mankin HJ, et al: Skeletal responses to enzyme replacement therapy in patients with Gaucher disease: what are the goals and expectations of treatment? Gaucher Clinical Perspectives 4(1):2-7, 1996

4. Pastores GM, Einhorn TA: Skeletal complications of Gaucher disease: pathophysiology, evaluation, and treatment. Seminars in Hematology 32(3, suppl 1):20-27, 1995

5. Brady RO, Barton NW, Grabowski GA. The role of neurogenetics in Gaucher disease. Arch Neurol. 1993;50:1212-1224.