Hematopoietic cell transplantation for severe MPS I in the first six months of life: The heart of the matter

Abstract

BackgroundHematopoietic cell transplantation (HCT) is accepted therapy for severe mucopolysaccharidosis type I (MPS IH). With implementation of newborn screening (NBS) for MPS I in the US, HCT may now occur earlier than 1–2 years of age and it might be assumed that cardiac issues will be fewer. To examine this hypothesis, we reviewed our records for any MPS IH infant who underwent HCT at ≤6 months of age. Study patientsPre- and (most recent) post-HCT cardiac echos and clinical courses were reviewed in all infants with MPS IH undergoing HCT at ≤6 months of age. Results7 MPS IH infants (4 M) who were diagnosed at median (range) (MEDRNG) of 14 (3, 22) days of life (DOL) by NBS [2] or because an older sib had MPS IH [5], began enzyme replacement therapy at MEDRNG of 48 (7, 62) DOL. First pre-HCT echo was performed at MEDRNG of 45 (0, 88) DOL. HCT (6 cord blood, 1 related) occurred at MEDRNG of 131 (105, 183) DOL with most recent echo at MEDRNG of 408 (10, 1897) days after HCT.Mitral regurgitation (≥mild) occurred before (2/7) and after (2/7) HCT; LVH (2/7) occurred after HCT; PFO was common before (5/7) and after (3/7) HCT. One infant had severely decreased function at initial echo and required ICU management. Another infant with a patent foramen ovale and indwelling central line required additional neuroimaging to determine the cause of a seizure. A final infant died unexpectedly 69 days post-HCT without evidence of occlusive coronary disease at autopsy. ConclusionsIn addition to the traditional phenotypic features of severe MPS I, newborns presenting for HCT have cardiac and non-cardiac problems unique to their young age. Recognition of these issues is essential for optimal outcomes.