The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I
Section snippets
Background
The rare autosomal recessive inherited disorder Mucopolysaccharidosis Type I (MPS I), results from deficit activity of the lysosomal enzyme α-l-iduronidase (MIM 252800). The resultant excess accumulation of sulphated dermatan and heparan species triggers multiple pathological cascades, ultimately generating damaging local inflammatory responses [1,2]. The severity of the enzymic impairment is the chief phenotypic determinant. Those with either severe or moderate impairment, traditionally
Methodology
A retrospective case note review was undertaken of all paediatric patients with MPS I treated in one of the three nationally commissioned paediatric tertiary specialist centres in England. The study involved anonymised data collected from case notes; ethics committee approval was not required. Good Clinical Practice standards were adhered to throughout.
Inclusion criteria were: diagnostic enzymology demonstrating a significant reduction in α-L-iduronidase activity; diagnosis prior to the age of
Results
Overall the notes of the 64 patients that had undergone HSCT and 24 patients that had enzyme replacement therapy that had been under regular review by the Paediatric centre were examined. In total 66 MPS I patients satisfying the inclusion criteria were identified. Of these 46 were transplanted (45 Hurler and 1 Hurler-Scheie) and 20 were treated with ERT (17 Hurler-Scheie patients and 3 Hurler patients diagnosed too late for transplant). Of the 18 HSCT patients excluded due to inability to
Discussion
This is the largest non-pharmaceutically supported case series of pulmonary function testing so far reported in paediatric MPS I patients. The duration of follow-up with a medium time of 12.4 years post HSCT and 14.4 years on ERT is also, to the authors' understanding, the longest thus far described. The serial spirometry performed demonstrates that all patients, regardless of therapeutic intervention, have a degree of restrictive lung disease. In the post HSCT group, 55% of patients had mild
Conclusion
This study indicates that despite current treatment modalities all Hurler and Hurler-Scheie patients develop a degree of restrictive lung disease. While this may not be as prominent clinical concern as in some of the other MPS diseases and indeed was improving in approximately a quarter of the patients reported here, it remains a potentially significant cause of morbidity. Further work is required to precisely delineate the degree of obstructive overlay that likely interacts with restrictive
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
Acknowledgements
Contribution: AB, PH, KMS, SAJ, SW originally conceived of the idea. JS, JM, OA, NPB, KT, RW helped data capture. NBW, SW and AAB analysed the data and all authors were involved in the review of the manuscript.
Funding: N/A.
Consent: No consent was required for this retrospective audit.
Guarantor: AAB.
References (30)
Anatomical changes and pathophysiology of the brain in mucopolysaccharidosis disorders
Mol. Genet. Metab.
(2018)The natural history of MPS I: global perspectives from the MPS I registry
Genet. Med.
(2014)- et al.
Respiratory manifestations in mucopolysaccharidoses
Paediatr. Respir. Rev.
(2011) Outcomes of long-term treatment with Laronidase in patients with Mucopolysaccharidosis type I
J. Pediatr.
(2016)Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase)
J. Pediatr.
(2004)A comparison of maximal voluntary ventilation and forced vital capacity in adolescent idiopathic scoliosis patients
Spine Deform.
(2019)The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with mucopolysaccharidosis type I
Mol. Genet. Metab.
(2007)Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The storage disease collaborative study group
Blood
(1998)Quality of life of hurler syndrome patients after successful hematopoietic stem cell transplantation
Blood Adv.
(2017)Anti-TNF-alpha therapy enhances the effects of enzyme replacement therapy in rats with mucopolysaccharidosis type VI
PLoS One
(2011)
The mucopolysaccharidoses: a clinical review and guide to management
Arch. Dis. Child.
Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure
Orphanet. J. Rare. Dis.
Characterization of pulmonary function impairments in patients with mucopolysaccharidoses--changes with age and treatment
Pediatr. Pulmonol.
Prevalence of obstructive sleep apnea in patients with mucopolysaccharidosis types I, II, and VI in a reference center
Sleep Breath.
Sleep-related breathing in children with mucopolysaccharidosis
J. Inherit. Metab. Dis.
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