title: Obstructive sleep apnea syndrome after hematopoietic stem cell transplantation in children with mucopolysaccharidosis type I.
abstract: BACKGROUND
  Obstructive sleep apnea syndrome (OSAS) is very common in mucopolysaccharidosis I (MPS I). Hematopoietic stem cell transplantation (HSCT) is the preferred treatment for patients with severe MPS I diagnosed early in life. The protective effect of HSCT on the development of long term OSAS is not known.
  
  
  METHODS
  Overnight polysomnography (PSG) and biomarker data were analyzed during the annual follow-up in consecutive MPS I patients treated with HSCT.
  
  
  RESULTS
  The data of 13 patients (6 boys) were analyzed. Median age at HSCT was 17 (range 14-19) months, median age at PSG was 9.0 (4.5-14.5) years, and median time elapsed since HSCT was 7.6 (2.4-13.2) years. A significant correlation was observed between time elapsed since HSCT and the apnea-hypopnea index (AHI, r(2)=0.493, p=+0.003) and the oxygen desaturation index (r(2)=0.424, p=+0.02). Patients older than 10 years of age had a higher mean AHI (25.8/h vs 1.4/h, p=0.0008), a lower mean pulse oximetry (94.7% vs 97.2%, p=0.01) and a higher mean hypopnea index (18.8 vs 0.71/h, p=0.016) as compared to those younger than 10 years of age. No correlation was observed between the AHI and the metabolic clearance, assessed by urine glycosaminoglycan (GAG) excretion and residual enzyme activity, although there was a positive trend for the urinary GAG/higher normal value for age ratio (p=0.09).
  
  
  CONCLUSIONS
  HSCT does not offer long term protection against OSAS in MPS I with OSAS being documented in all patients after a time elapse since HSCT exceeding 10 years. The potential benefit of additional enzyme replacement therapy needs to be assessed.
authors.affiliation: Pediatric Noninvasive Ventilation and Sleep Unit, AP-HP, Hôpital Necker Enfants-Malades, Paris, France; Physiological Department and INSERM U1046 UMR 9214, University of Montpellier, Montpellier, France. Electronic address: johanmoreauchu@gmail.com.
authors.forename: Johan
authors.initials: J
authors.lastname: Moreau
authors.affiliation: Reference Center for Inherited Metabolic Disease (MeMEA) and IMAGINE Institute, Hôpital Necker Enfants-Malades, Paris, France. Electronic address: anais.brassier@aphp.fr.
authors.forename: Anais
authors.initials: A
authors.lastname: Brassier
authors.affiliation: Pediatric Noninvasive Ventilation and Sleep Unit, AP-HP, Hôpital Necker Enfants-Malades, Paris, France; Paris Descartes University, Paris, France. Electronic address: alessandro.amaddeo@aphp.fr.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Amaddeo
authors.affiliation: Pediatric Immunology and Hematology Department, Hôpital Necker Enfants-Malades, Paris, France. Electronic address: benedicte.neven@aphp.fr.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Neven
authors.affiliation: Metabolic Biochemistry Department, P-HP, Hôpital Necker Enfants-Malades, Paris, France. Electronic address: catherine.caillaud@aphp.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Caillaud
authors.affiliation: Metabolic Biochemistry Department, P-HP, Hôpital Necker Enfants-Malades, Paris, France. Electronic address: allel.chabli@aphp.fr.
authors.forename: Allel
authors.initials: A
authors.lastname: Chabli
authors.affiliation: Pediatric Noninvasive Ventilation and Sleep Unit, AP-HP, Hôpital Necker Enfants-Malades, Paris, France. Electronic address: martafbm@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernandez-Bolanos
authors.affiliation: Pediatric Noninvasive Ventilation and Sleep Unit, AP-HP, Hôpital Necker Enfants-Malades, Paris, France. Electronic address: jorge.olmo.arroyo@gmail.com.
authors.forename: Jorge
authors.initials: J
authors.lastname: Olmo
authors.affiliation: Reference Center for Inherited Metabolic Disease (MeMEA) and IMAGINE Institute, Hôpital Necker Enfants-Malades, Paris, France. Electronic address: vassili.valaya@aphp.fr.
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.affiliation: Pediatric Noninvasive Ventilation and Sleep Unit, AP-HP, Hôpital Necker Enfants-Malades, Paris, France; Paris Descartes University, Paris, France; Inserm U 955, Team 13, Créteil University, Paris XII, Créteil, France. Electronic address: brigitte.fauroux@aphp.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Fauroux
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000652:urine; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008059:Mucopolysaccharidosis I / Q000150:complications / Q000175:diagnosis* / Q000628:therapy* / Q000652:urine; D010092:Oximetry; D017286:Polysomnography; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000175:diagnosis* / Q000628:therapy* / Q000652:urine
chemical_list: D006025:Glycosaminoglycans
keywords: Child; Hematopoietic stem cell transplantation; Mucopolysaccharidosis I; Obstructive sleep apnea syndrome; Polysomnography; Sleep disordered breathing