The patient is 30 y.o. woman who presents to her primary physician complaining of weight loss, fatigue, abdominal enlargement, gum bleeding, and episodic bone pain, particularly in her legs. She also describes an episodic migratory polyarthritis affecting her hands, feet, and knees that has become increasingly severe over the last few months. She now has increased pain in her knees while standing. Physical examination reveals a protuberant abdomen with marked hepatosplenomegaly; articular examination is unremarkable. Laboratory evaluation reveals a HCT of 29 and a platelet count of 40,000. Suspecting leukemia, a bone marrow biopsy was promptly performed, which revealed infiltration of enlarged lipid-laden histiocytes. Plain radiographs of the legs were obtained, and a diagnostic test was ordered.
Radiographs of femurs demonstrate expansion of the contour of the femoral shafts with marked cortical thinning (red arrow). The Erlenmeyer flask deformity is noted, with the development of a “convex” surface in the distal femora. Additionally, there is evidence of avascular necrosis (yellow arrow) with sclerosis and radiolucencies in the femoral condyles. These features are also noted on a set of films obtained from a child being treated at the same hospital. The right pediatric hip shows AVN (green arrow) with deformity of the articular surface of the femoral head, and the knee films show the classic Erlenmeyer deformity (red arrow).
Diagnosis and Discussion
Correct Diagnosis: Gauchers Disease,
Type 1 (b-glucocerebrosidase deficiency)
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.
- 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.