Hematopoietic cell transplantation for Mucopolysaccharidosis I in the presence of decreased cardiac function

Nishitha R Pillai; Sara A Elsbecker; Ashish O Gupta; Troy C Lund; Paul J Orchard; Elizabeth Braunlin

doi:10.1016/j.ymgme.2023.107669

Hematopoietic cell transplantation for Mucopolysaccharidosis I in the presence of decreased cardiac function

Mol Genet Metab. 2023 Nov;140(3):107669. doi: 10.1016/j.ymgme.2023.107669. Epub 2023 Jul 27.

Authors

Nishitha R Pillai¹, Sara A Elsbecker², Ashish O Gupta³, Troy C Lund³, Paul J Orchard³, Elizabeth Braunlin⁴

Affiliations

¹ Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, MN, USA. Electronic address: Pilla125@umn.edu.
² Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, MN, USA.
³ Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁴ Division of Pediatric Cardiology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.

PMID: 37542767
DOI: 10.1016/j.ymgme.2023.107669

Abstract

Background: Severe mucopolysaccharidosis type I, (MPS IH) is a rare inherited lysosomal disorder resulting in progressive storage of proteoglycans (GAGs) in central nervous system and somatic tissues and, if left untreated, causing death within the first decade of life. Hematopoietic cell transplantation (HCT) arrests many of the features of MPS IH but carries a 10-15% risk of mortality. Decreased cardiac function can occur in MPS IH and increase the risk of HCT.

Methods: Retrospective chart review was performed to determine the long-term outcome of individuals evaluated for HCT with MPS IH who had decreased cardiac function as measured by cardiac echocardiogram (echo) and ejection fraction (EF) of <50% at the time of initial evaluation.

Results: Six patients ranging in age from 1 week to 21 months (median: 4 months) had EFs ranging from 25 to 47% (median: 32%) at diagnosis and were initiated on enzyme replacement therapy (ERT) with improvement in EF in three patients by 5 months. The remaining three patients continued to have EFs <50% and continuous milrinone infusion was added in the pre-HCT period. On average, milrinone infusion was able to be discontinued post-HCT, prior to hospital discharge, within a mean of 37 days. Five patients survived HCT and are alive today with normal EFs. One patient receiving milrinone died of sepsis during HCT with a normal EF.

Conclusion: Decreased cardiac systolic function in infants with MPS IH that fails to normalize with ERT alone may benefit from the addition of continuous milrinone infusion during HCT.

Keywords: Cardiomyopathy; Enzyme replacement therapy; Hurler syndrome; MPS IH; Milrinone; Newborn screening; Reduced cardiac function.

MeSH terms

Enzyme Replacement Therapy / methods
Heart
Hematopoietic Stem Cell Transplantation* / methods
Humans
Infant
Infant, Newborn
Milrinone / therapeutic use
Mucopolysaccharidosis I* / diagnosis
Retrospective Studies

Substances

Milrinone