RT Journal Article
SR Electronic
T1 Obstructive sleep apnoea in mucopolysaccharidosis I: The role of phenotype and treatment on clinical outcome
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P4927
VO 44
IS Suppl 58
A1 Ricky Pal
A1 Iain Bruce
A1 Robert Wynn
A1 Simon Jones
A1 Brian Bigger
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P4927.abstract
AB ObjectivesMucopolysaccharidosis I (MPSI) is a multisystem inherited lysosomal storage disorder, with death often occurring in the second decade of life due to airway complications. Therapeutic interventions include haemopoietic stem cell transplantation (HSCT) for the severe Hurler phenotype and enzyme replacement therapy (ERT) for the attenuated Hurler-Scheie form. The severity of obstructive sleep apnoea (OSA) with respect to phenotype and treatment is poorly defined. We present data on the largest MPSI cohort described to date.MethodsClinical data, including 165 sleep studies, were collected in 69 MPSI patients from 6 months pretreatment to 16 years post-treatment (mean follow-up 2.5 yrs). Forty-one patients received HSCT, while 39 received ERT.ResultsThe incidence of OSA in our cohort is 56%. HSCT in Hurler patients results in a significantly greater disease correction, when assessed by oxygen desaturation index 4% (ODI4%) and saturation nadir, compared to attenuated patients treated with ERT alone (ODI4% 7.5 vs. 12.8, p=0.016). However, with increasing age and duration post-HSCT, continued airway disease progression occurs despite metabolic correction. Stratified by donor type, patients receiving HSCT demonstrate greater biochemical and airway correction when receiving grafts from unrelated donors with two copies of the missing IDUA gene as opposed to heterozygote, related donors expressing one gene copy (mean, enzyme: 39 vs. 25umol/g/hr. ODI4% 6.6 vs 8.5).ConclusionHSCT with a matched-unrelated donor results in optimal correction of OSA in MPSI. However, continued disease progression is seen in all patients, worse in individuals receiving ERT versus HSCT.