Fatal and Unanticipated Cardiorespiratory Disease in a Two-Year-Old Child with Hurler Syndrome Following Successful Stem Cell Transplant

Abstract

A 2-year-old female with Hurler syndrome (mucopolysaccharidosis type 1) died suddenly within 3 months of successful unrelated fully matched cord blood transplant, having received weekly enzyme replacement therapy (ERT) prior to transplant. Though an infectious aetiology was clinically suspected to be the cause of her unanticipated acute deterioration and untimely demise, autopsy findings suggested that a combination of pre-existing but sub-clinical Hurler related cardiopulmonary pathology and superimposed transplant related pulmonary venopathy as the basis of her death. This case highlights the limitations of ERT in ameliorating cardiorespiratory disease and the failure of standard pretransplant investigations to detect significant abnormality related to her underlying condition. It also reinforces the importance of autopsy in explaining unanticipated events.

The Carotid Intima-Media Thickness and Arterial Stiffness of Pediatric Mucopolysaccharidosis Patients Are Increased Compared to Both Pediatric and Adult Controls

“…Lysosomal accumulation of GAGs causes multi-systemic disease, including cognitive impairment of variable severity, hepatosplenomegaly, skeletal dysplasia with degenerative arthritis, cardiac valvular dysplasia, and arterial vascular disease [1]. MPS patients frequently die of cardiovascular disease, which often worsens despite development of treatments such as hematopoietic stem cell transplantation (HSCT) and intravenous enzyme replacement therapy (ERT) [2,3,4,5,6,7,8]. …”