Skeletal abnormalities and successful hematopoietic stem cell transplantation in patients with reticular dysgenesis

摘要

Reticular dysgenesis (RD) is a rare autosomal recessive disorder caused by mutations in the adenylate kinase 2 gene (AK2) clinically characterized by bilateral sensorineural deafness and a unique combination of severe combined immunodeficiency and agranulocytosis, which predispose infants to severe life-threatening infections. Analysis of bone marrow consistently shows a maturation arrest at the promyelocyte stage while sparing the erythroid and megakaryocytic lineages. Maturation of lymphocytes is also severely affected, with resultant markedly reduced circulating T- and B-cell numbers. The thymus appears dysplastic, with an absence of Hassall corpuscles. Granulocyte colony-stimulating factor (G-CSF) was shown to have little or no benefit in patients with RD, but hematopoietic stem cell transplantation (HSCT) might be curative. Experience is very limited, especially when considering the short follow-up times and the lack of molecular diagnosis in most previously reported cases.