Umbilical cord blood transplantation in Hurler syndrome using busulfan, fludarabine, clofarabine, rATG conditioning regimen

Abstract

Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal disorder caused by deficiency of iduronate-2-sulfatase enzyme activity. Affected males experience progressive disease including airway obstruction, skeletal deformities, cardiomyopathy and, in most cases, neurological decline. Enzyme replacement therapy (ERT) with idursulfase (a recombinant form of human iduronate-2-sulfatase) has shown encouraging results in modifying the non-CNS manifestations. Best results are observed with earlier initiation of ERT. Hematopoietic stem cell transplantation (HSCT) may modify CNS and non-CNS manifestations.Wepresent a family of three affected brothers. The oldest brother was diagnosed at age six years and received ERT for four years. He is now 13. The middle brother was diagnosed at age two and a half years and has continued to receive ERT since then. He is now 11 and has milder non-CNS involvement compared to his older brother. His cognitive function is significantly impaired. The youngest brother was diagnosed prenatally, received ERT starting at four months of age, and underwent a mismatched unrelated umbilical cord blood transplant at tenmonths of age. He is now two and a half years old. The progression of his disease has been slowed compared to his brothers’, and he is showing gains in developmental milestones. The three brothers have received different treatments at different ages, and show varying rates of disease progression. Their treatment and clinical histories will be summarized.