Long-Term Neurodevelopmental Outcome of Patients with Mucopolysaccharidosis-1H (MPS-1H) following Hematopoietic Stem Cell Transplantation (HSCT)

Background/Purpose: HSCT is considered standard of care for MPS-1H diagnosed in infancy, as it has the potential to deliver the deficient enzyme α-L-iduronidase to the CNS. We assessed neurodevelopmental outcome more than 10 years after HSCT in a cohort of patients, in whom we had previously shown developmental progress but ongoing mild to moderate psychomotor retardation on short-term follow-up (Lücke et al Dev Med Child Neurol (2007)).

Methods: Five patients (4 females, 1 male) underwent HSCT at a median age of 1.91 years (0.82–2.99). They were studied after a median follow-up time of 11.51 years (10.02–13.64). Besides physical and neurological examination, patients underwent qualitative assessment with either WISC-IV (n = 2) or WPPSI-III (n = 2). Pegboard test (ZNM) could be performed in three of the five patients. In one patient, no standardized testing could be performed.

Results: All patients showed further developmental progress, with two of the five patients now having a global IQ within the normal range (105 and 130). Median head circumference decreased from +2.21 SDS at the time of HSCT to +2.04 SDS. Speech development was impaired in two, and one child showed no expressive language. All children showed corneal clouding, pegboard test was abnormal in one of the three patients, and sensorineural hearing in two of the five patients. Musculoskeletal problems including kyphoscoliosis and contractures were present in all patients; three of the five patients were unable to walk.

Conclusion: Following HSCT, patients with MPS-1H show continuous but variable developmental progress, some even an above-average cognition, despite ongoing problems regarding especially musculoskeletal tissues.