The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I.

Respiratory outcomes in Mucopolysaccharidosis Type I (MPS I), have mainly focused on upper airway obstruction, with the evolution of the restrictive lung disease being poorly documented. We report the long-term pulmonary function outcomes and examine the potential factors affecting these in 2 cohorts of MPS I patients, those who have undergone Haematopoietic Stem Cell Transplantation (HSCT) and those treated with Enzyme Replacement Therapy (ERT). The results were stratified using the American Thoracic Society (ATS) guidelines. 66 patients, capable of adequately performing testing, were identified by a retrospective case note review, 46 transplanted (45 Hurler, 1 Non-Hurler) and 20 having ERT (17 Non-Hurler and 3 Hurler diagnosed too late for HSCT). 5 patients died; 4 in the ERT group including the 3 Hurler patients. Overall 14% of patients required respiratory support (non-invasive ventilation (NIV) or supplemental oxygen)) at the end of follow up. Median length of follow-up was 12.2 (range = 4.9-32) years post HSCT and 14.34 (range = 3.89-20.4) years on ERT. All patients had restrictive lung disease. Cobb angle and male sex were significantly associated with more severe outcomes in the HSCT cohort, with 49% having severe to very severe disease. In the 17 Non-Hurler ERT treated patients there was no variable predictive of severity of disease with 59% having severe to very severe disease. During the course of follow up 67% of the HSCT cohort had no change or improved pulmonary function as did 52% of the ERT patients. However, direct comparison between therapeutic modalities was not possible. This initial evidence would suggest that a degree of restrictive lung disease is present in all treated paediatrically diagnosed MPS I and is still a significant cause of morbidity, though further stratification incorporating diffusing capacity for carbon monoxide (DLCO) is needed.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr. A Broomfield declares travel assistance from Takeda Pharmaceutical, Sanofi and Biomarin Pharmaceutical and consulting fees from Sanofi, unrelated to this work. Dr. A Ghosh declares travel assistance from Biomarin Pharmaceutical and honoraria from Alexion Pharmaceuticals, unrelated to this work. Dr. KM Stepien has received travel grants from BioMarin, Genzyme, Alexion, Takeda Pharmaceutical and honoraria from Biomarin Pharmaceutical Chiesi, Sanofi, Orchard Therapeutics and Takeda unrelated to this work. K Tylee declares prior travel assistance from Biomarin Pharmaceutical, unrelated to this work. Dr. S Jones declares consultancy for Genzyme, Shire, Alexion Pharmaceuticals, Orchard Therapeutics, Denali Therapeutics, and Ultragenyx Pharmaceutical, unrelated to this work. All other authors declare no conflict of interest.