Newborn Screening for Hurler Syndrome Facilitates Early Transplant and Good Outcomes.

Background: Hematopoietic cell transplantation (HCT) is the standard of care treatment for children with Hurler syndrome (HS). This study describes the impact of newborn screening (NBS) on HCT outcomes for these patients.

Methods: Retrospective study of HS patients diagnosed through NBS and referred to Duke from 2017 to 2023. Patients received a myeloablative busulfan-based regimen and unrelated umbilical cord blood HCT, with cyclosporine and mycophenolate for graft-versus-host-disease prophylaxis.

Results: Patients (N =9) were transplanted at a median age of 5.2 months and median weight of 7.8 kg. Median reinfused total nucleated cell was 14.8 × 10/kg. The median times to neutrophil and platelet engraftment were 17 and 48 days, respectively. No primary graft failures or rejections were observed. Post-HCT complications included sinusoidal obstructive syndrome, microangiopathy and autoimmune hemolytic anemia. At median follow-up of 29.1 months (range 4.1-72.2), 8 of 9 patients were alive with normal alpha-L-iduronidase (IDUA) levels, Lansky scores of 90-100%, and developing milestones. One patient died due to autoimmune hemolytic anemia on day +139 (with normal IDUA level and >98% donor chimerism at day +100).

Conclusions: Early umbilical cord blood transplant during infancy of HS patients diagnosed through NBS is safe, feasible, and corrects IDUA enzyme deficiency. Follow-up studies will ascertain the long-term benefits of this approach.