Long term follow-up after haematopoietic stem cell transplantation for mucopolysaccharidosis type I-H: a retrospective study of 51 patients

Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by alpha-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) is the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8-16.5) for 51 MPS I-H patients who underwent HSCT between 1986 and 2018 in France. 4 patients died from complications of HSCT and one from disease progression. Complete chimerism and normal alpha-L-Iduronidase activity were obtained in 84% and 71% of patients respectively. No difference of outcomes was observed between bone marrow and cord blood stem cell sources. All patients acquired independent walking and 91% and 78% acquired intelligible language or reading and writing. Intelligence Quotient evaluation (n = 23) showed that 69% had IQ & GE; 70 at last follow-up. 58% of patients had normal or remedial schooling and 62% of the 13 adults had good socio-professional insertion. Skeletal dysplasia as well as vision and hearing impairments progressed despite HSCT, with significant disability. These results provide a long-term assessment of HSCT efficacy in MPS I-H and could be useful in the evaluation of novel promising treatments such as gene therapy.

Automated summary

MPS I-H is a rare lysosomal storage disorder caused by alpha-L-Iduronidase deficiency. Early hematopoietic stem cell transplantation (HSCT) is the only available therapeutic option to preserve neurocognitive functions. A long-term follow-up of MPS I-H patients who underwent HSCT showed good outcomes in terms of chimerism, enzyme activity, language acquisition, and socio-professional insertion. However, skeletal dysplasia and sensory impairments progressed despite HSCT, indicating the need for further treatment options such as gene therapy.