Gaucher's disease
Objectives- Describe the pathophysiology of Gaucher's disease
- Describe the most frequent orthopaedic problems associated with Gaucher's disease
- Describe radiographic features of Gaucher's disease
- Discuss the prognosis for Gaucher's disease
Discussion
Gaucher's disease is a lysozomal storage disease, characterized by intracellular accumulation of glucocerebroside, an important component of cell wall membranes. The accumulation of cerebroside occurs in macrophages, found primarily in the spleen, liver, and bone marrow. The enzymatic defect is a deficiency of glucocerebrosidase, and results from one or several common mutation sites, some producing more severe deficiency than others. The genetic pattern is autosomal recessive. Type I, the most common, is particularly prevalent among descendants of Asheknazi Jews. Effects are most evident in the spleen, liver, and bones. This type has also been reported in Japanese. Type II, the acute neuronopathic type generally causes death by age 2. Type III, the chronic neuronopathic type, has features of group I with slowly progressive neurologic dysfunction.
Age of diagnosis is quite variable, and appears related to the genetic focus of the enzymatic deficiency. Common presenting symptoms are related to coagulation problems, with splenomegaly. Bone pain or fracture is an uncommon (13%) presenting symptom.
Skeletal changes have been well described, and include the classic "Erlenmeyer flask" shape of the metaphyses, especially in the distal femora; but also osteopenia, cortical thinning, avascular necrosis, and pathologic fracture. Gaucher crises are common, similar to sickle cell crisis, and also mimic osteomyelitis. They result from sudden bleeds into the marrow space, with sudden rise in marrow pressure. As a result, bone scintigraphy often reveals decreased uptake initially, followed by increased uptake during the repair phase. Steroids have been reported to alleviate symptomatology during crises. Pathologic fractures are prevalent in the lower extremities and spine, with occasional kyphosis resulting, sometimes threatening neurologic function. Ostenecrosis of the femoral heads does not appear to be as debilitating as in sickle cell disease. Favorable reports have been reported with enzyme therapy with aglucerase, with reversal of skeletal changes reported. There presently is a Gaucher registry to better accumulate data on the condition and response to treatment, which at this point appears to be promising.
References
- Beutler E, Gelbart T. Gaucher disease mutations in non-Jewish patients. British Journal of Haematology 1993; 85( 2): 401-5.
- Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, et al. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Archives of Internal Medicine 2000; 160( 18): 2835-43.
- Cohen IJ, Kornreich L, Mekhmandarov S, Katz K, Zaizov R. Effective treatment of painful bone crises in type I gaucher's disease with high dose prednisolone. Archives of Disease in Childhood 1996; 75( 3): 218-22.
- Cohen IJ, Katz K, Kornreich L, Horev G, Frish A, Zaizov R. Low-dose high-frequency enzyme replacement therapy prevents fractures without complete suppression of painful bone crises in patients with severe juvenile onset type I Gaucher disease [see comments]. Blood Cells, Molecules, & Diseases 1998; 24( 3): 296-302.
- Dolen EG, Berdon WE, Ruzal-Shapiro C. "Cold bone scans" as a sign of hemorrhagic infarcts of the spine in Gaucher's disease. Pediatric Radiology 1997; 27( 6): 514-6.
- Hill SC, Parker CC, Brady RO, Barton NW. MRI of multiple platyspondyly in Gaucher disease: response to enzyme replacement therapy. Journal of Computer Assisted Tomography 1993; 17( 5): 806-9.
- Ida H, Rennert OM, Iwasawa K, Kobayashi M, Eto Y. Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation. Human Genetics 1999; 105( 1-2): 120-6.
- Kaplan P, Mazur A, Manor O, Charrow J, Esplin J, Gribble TJ, et al. Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase. Journal of Pediatrics 1996; 129( 1): 149-53.
- Katz K, Mechlis-Frish S, Cohen IJ, Horev G, Zaizov R, Lubin E. Bone scans in the diagnosis of bone crisis in patients who have Gaucher disease [published erratum appears in J Bone Joint Surg Am 1991 Jun; 73( 5): 791]. Journal of Bone & Joint Surgery -American Volume 1991; 73( 4): 513-7.
- Katz K, Sabato S, Horev G, Cohen IJ, Yosipovitch Z. Spinal involvement in children and adolescents with Gaucher disease. Spine 1993; 18( 3): 332-5.
- Katz K, Horev G, Grunebaum M, Yosipovitch Z. The natural history of osteonecrosis of the femoral head in children and adolescents who have Gaucher disease. Journal of Bone & Joint Surgery -American Volume 1996; 78( 1): 14-9.
- Katz K, Kornreich L, Horev G, Ziv N, Soudry M, Cohen IJ. Involvement of the foot and ankle in patients with Gaucher disease. Foot & Ankle International 1999; 20( 2): 104-7.
- Kocher MS, Hall JE. Surgical management of spinal involvement in children and adolescents with Gaucher's disease. Journal of Pediatric Orthopedics 2000; 20( 3): 383-8.
- Pastores GM, Hermann G, Norton KI, Lorberboym M, Desnick RJ. Regression of skeletal changes in type 1 Gaucher disease with enzyme replacement therapy. Skeletal Radiology 1996; 25( 5): 485-8.
- Rice EO, Mifflin TE, Sakallah S, Lee RE, Sansieri CA, Barranger JA. Gaucher disease: studies of phenotype, molecular diagnosis and treatment. Clinical Genetics 1996; 49( 3): 111-8.
- Sidransky E, Tayebi N, Ginns EI. Diagnosing Gaucher disease. Early recognition, implications for treatment, and genetic counseling. Clinical Pediatrics 1995; 34( 7): 365-71.
- Stowens DW, Teitelbaum SL, Kahn AJ, Barranger JA. Skeletal complications of Gaucher disease. Medicine 1985; 64( 5): 310-22.
- Tauber C, Tauber T. Gaucher disease--the orthopaedic aspect. Report of seven cases. Archives of Orthopaedic & Trauma Surgery 1995; 114( 3): 179-82.
May 16-19, 2012 in Denver, CO
