[Show abstract][Hide abstract] ABSTRACT: Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood ( approximately 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients.
[Show abstract][Hide abstract] ABSTRACT: Rituximab, an anti-CD20 chimeric antibody, is the first monoclonal agent to be used in the therapy of cancer. It has been hailed as one of the most important therapeutic developments of the decade. While transient peripheral B cell depletion is common after rituximab therapy, immunoglobulin levels are generally not affected. This is because CD20 is expressed on pre-B and mature B lymphocytes but not on stem cells or plasma cells. Two adult patients with pre-existing primary antibody deficiency who presented with recurrent infections immediately following rituximab use for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) are described. Both were previously treated with various immunosuppressive agents without any notable infective problems. However, a few weeks after treatment with rituximab, these patients presented with clinically significant immunodeficiency requiring intravenous immunoglobulin replacement therapy. This striking temporal relationship between rituximab administration and onset of infections suggests that rituximab has accelerated the presentation of immune deficiency in these patients. Increased vigilance around the use of newer immunomodulatory agents such as rituximab is recommended.
[Show abstract][Hide abstract] ABSTRACT: Cartilage-hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia characterised by short limbed short stature, hypoplastic hair growth, and impaired cell mediated immunity and erythrocyte production. The syndrome is exceptionally prevalent among the Finns and among the Old Order Amish in the United States; sporadic cases have been reported from other countries. An epidemiological and genetic study of CHH in Finland showed 107 patients, 46 males and 61 females, in 85 families. Eighteen of them had died, seven before the age of 1 year. The living patients ranged in age from 1 to 51 years, median 21 years. The incidence was estimated to be 1:23,000 live births. Consanguinity was found in two families and interfamilial relationships in 20 families. Geographical distribution of the birth places of the patients and their great grandparents showed accumulation in a small area in western Finland and regional clusters were seen in other parts of the country as well. The result of the segregation analysis was in accordance with recessive inheritance with reduced penetrance.
Journal of Medical Genetics 10/1992; 29(9):652-5. DOI:10.1136/jmg.29.9.652 · 5.64 Impact Factor
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