Utility of both bone marrow and renal transplants in the management of individuals with Schimke immunooseous dysplasia

Abstract

Schimke immunoosseous dysplasia (SIOD) is a rare autosomal recessive osteochondrodysplasia that presents in infancy or childhood. It is characterized by spondyloepiphyseal dysplasia, growth failure, proteinuria progressing to renal failure, characteristic facial features, lymphopenia with immunodeficiency, occasional pancytopenia, cerebral vascular disease, and autoimmune dysfunction. It is associated with significant early morbidity and mortality with death during childhood in classic cases. The underlying molecular etiology is unknown. There is no effective curative treatment. While dialysis and renal transplantation have successfully managed the renal disease, much of the disease related morbidity and early mortality is due to cell-mediated immunodeficiency that has been refractory to medical therapy. Given the utility of bone marrow transplant (BMT) in the treatment of other immunodeficiency and hypoplastic bone marrow states, we successfully utilized BMT for the management of SIOD in a boy who presented with severe marrow hypoplasia and immunodeficiency. BMT had not been reported for the management of SIOD. The patient was a six-year-old boy who initially presented in infancy with short stature and gastrointestinal problems. He later displayed classic features of SIOD, including progressive renal disease. His renal disease progressed after BMT. He subsequently underwent a related donor renal transplant 18 months after BMT. At 20 months after BMT and 2 months following renal transplant he demonstrates significantly improved immune function, reconstitution of all marrow derived cell lineages, good renat function, and, importantly, an improved sense of overall well being with increased appetite and activity. He had no adverse chronic neurological sequelae. Based on the excellent outcome of our patient to date, we predict that, until better targeted therapies are developed, bone marrow transplantation in addition to renal transplantation may provide the most effective therapy currently available for severe SIOD, decreasing the morbidity in, and increasing the lifespan of, children with this disorder.