Radiology Rounds
Round # 13
Correct Diagnosis: Gauchers Disease,
Type 1 (b-glucocerebrosidase deficiency)
Discussion:
Gauchers Disease is an autosomal recessive condition caused by a deficiency in the lysosomal enzyme b-glucocerebrosidase. Three types have been described, but Type 1 (non-neuronopathic, adult onset) is by far the most common, being seen in over 90% of patients in a large Gaucher registry, with a mean age of onset of around 20 years old. Types 2 and 3 are rare and occur in infancy to very early childhood. The main clinical manifestations of the disease are caused by infiltration of hematopoetic organs with "Gaucher cells" (enlarged lipid-laden histiocytes). This infiltration leads to the hepatosplenomegaly, anemia, thrombocytopenia, and bone pain often seen in this condition. The diagnosis is made by confirming deficient b-glucocerebrosidase activity from patient leukocytes in an in vitro assay.
Bone symptoms occur in the majority of patients with Gauchers disease, and abnormalities on plain radiographs are nearly universal in affected patients. The spectrum of bony involvement includes diffuse osteopenia with pathologic fractures, osteonecrosis (including epiphyseal involvement in children), bone infarcts, bone pain, and occasionally a migratory polyarthritis of unclear etiology. The disease primarily affects the long bones and the vertebrae, but nearly any bone can be affected over the course of the disease if left untreated. Defects in bone modeling are frequently seen, resulting in the classic "erlenmyer flask deformity" noted on plain radiographs. Though the Erlenmyer flask deformity has a wide differential diagnosis, its combination with epiphyseal osteonecrosis on the same film is highly suggestive of Gauchers disease. Bone scanning and MRI can be useful adjunctive imaging studies to document marrow edema and infiltration.
Gauchers disease can be successfully treated with enzyme replacement therapy (ERT). There are currently 2 intravenous preparations of b-glucocerebrosidase (alglucerase and imiglucerase), and both are widely available. Bone symptoms, and even bony deformities, often regress significantly after ERT is instituted.
References:
- Charrow J, Esplin JA, Gribble TJ, Kaplan P, Kolodny EH, Pastores GM, Scott CR, Wappner RS, Weinreb NJ, Wisch JS. Gaucher disease: recommendations on diagnosis, evaluation, and monitoring. Arch Intern Med 158(16):1754-60, 1998.
- Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ, Zimran A. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 160(18):2835-43, 2000.
- Resnick D. Lipidoses, Histiocytoses, and Hyperlipoproteinemias. In: Resnick D, ed. Diagnosis of Bone and Joint Disorders 4th ed. Philadelphia, London, Toronto, Montreal, Sydney, Tokyo: Saunders, 2234-2245, 2002.
