Developmental outcome in five children with Hurler syndrome after stem cell transplantation: a pilot study.

Hurler syndrome (mucopolysaccharidosis type 1H; MPS1H) is a lysosomal storage disease caused by a deficiency of alpha-L-iduronidase activity. The natural course of this neurodegenerative disease inevitably leads to premature death within the first 10 years of life. Enzyme replacement therapy is effective in correcting the enzymatic deficiency of organs other than the central nervous system. Hematopoietic stem cell transplantation (SCT) is the only treatment known to prevent psychomotor deterioration. However, the classical transplantation protocols resulted in a high incidence of graft failure and regimen-related toxicity. Recently, we published a well-tolerated, fludarabine-based, radiation-free conditioning regimen for SCT in patients with Hurler syndrome. Here we report the developmental outcome (assessed by the Denver Developmental Screening Test before and yearly after SCT) of four females and one male with MPS1H (mean age at last follow-up 71mo, range 42-87mo) treated in accordance with this strategy. Mean age at SCT was 25 months (range 10-36mo). All children were engrafted and in ambulatory care. They all showed psychomotor development without neurodegeneration. In all patients, after SCT a regression of intracranial lesions could be seen that paralleled the psychomotor improvements. SCT led to a relative reduction of head circumference in all cases.