Haematopoietic stem cell transplantation in inborn errors of metabolism

This review summarizes the main results of haematopoietic stem cell transplantation (HSCT) in selected inborn errors of metabolism (IEMs).

Early diagnosis and immediate referral to an IEM specialist is of paramount importance to improve clinical outcome: patients who are transplanted early or in their presymptomatic phase generally achieve better correction of their somatic symptoms and neurocognitive development. Long-term outcome in children with Hurler syndrome is influenced by age at HSCT, baseline clinical status and post-HSCT enzyme levels. Myeloablative Busulfan-based conditioning regimens with therapeutic drug monitoring are recommended to achieve full donor engraftment and more robust enzyme delivery after HSCT. Gene therapy can lead to production of supranormal enzyme levels, and preliminary clinical results are also promising in IEMs historically not responsive to allogeneic HSCT.

Allogeneic HSCT has largely contributed to the improved survival and quality of life of many children affected by IEMs. Neonatal screening could enable earlier HSCT, and this might significantly reduce residual disease burden and improve clinical outcome. Novel strategies, such as gene therapy, have shown encouraging clinical results in selected IEMs and might become more widely available in the future, with potentially better enzyme delivery and reduced transplant-related toxicity.