Evaluation of sleep‐disordered breathing and its relationship with respiratory parameters in children with mucopolysaccharidosis Type IVA and VI

Abstract

The aims of the study were to evaluate the prevalence of sleep-disordered breathing (SDB) by using polysomnography (PSG) in children with MPS IVA and MPS VI who underwent enzyme replacement therapy (ERT) and to analyze the effect on SDB of having upper airway surgery, pulmonary functions, and exercise capacity. A retrospective cross-sectional study was conducted on patients with MPS IVA (n:17) and MPS VI (n:11) aged under 19 years who underwent polysomnography. Descriptive and nonparametric analyses were performed for demographic, PSG, pulmonary function and exercise capacity variables. The frequency of sleep apnea in the study sample was 85.7% (24/28). Four patients (14.3%) had no sleep apnea, 15 (53.6%) had mild, and nine (32.1%) had moderate-to-severe sleep apnea. Two patients (7.1%) had central sleep apnea and 22 had obstructive sleep apnea (OSA) (78.6%). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were negatively correlated to apnea-hypopnea index (AHI) (r = À0.594, p = .009; r = À0.636, p = .005, respectively). Despite ERT and previous upper airway surgery, the prevalence of OSA was high in patients with MPS IVA-MPS IV, emphasizing the importance of PSG screening for sleep disorders. Pulmonary function tests may be useful for predicting sleep apnea in patients with MPS IVA and MPS VI.

Pediatric Sleep Respiratory Disorders: A Narrative Review of Epidemiology and Risk Factors

“…Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by an error in the catabolism of glycosaminoglycans (GAGs), with a consequent build-up of mucopolysaccharides in multiple tissues [ 109 ]. An increased prevalence (range, 68–95%) of OSA, demonstrated by polysomnography and nocturnal oximetry, is reported in infants with MPS, often associated with sustained hypoventilation and/or central apnea [ 12 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. Obstructive SDB occurs as a consequence of increased upper airway resistance due to the multilevel skeletal, oral, adenotonsillar, laryngeal, and tracheal involvement, reported in all MPS types, with minor relevance for MPS III [ 109 , 118 ].…”

“…Until a few years ago, the literature describing the incidence of OSAS in MPS was mainly based on cross-sectional analyses of small cohorts of patients prior to the initiation of treatment (haemopoietic stem cell transplantation—HSCT, enzyme replacement therapy—ERT) and without standardized criteria to define OSA [ 112 , 113 ]. More recent studies, methodologically more homogeneous (OSA defined for an obstructive AHI > 1.5/h), confirm a prevalence of OSA, ranging from 69.8% to 95.2% [ 115 , 116 , 117 ]. In a recent meta-analysis in 2021, the prevalence and profile of sleep disorders in rare genetic syndromes confirmed that SDB was most prevalent in MPS disorders (72–77%) compared to other syndromes mentioned above, such as DS and PWS.…”

“…OSA may persist after surgery or manifest despite it, due to multiple site of GAG deposition. Ademhan Tural et al, in a retrospective cross-sectional study on 17 children suffering from MPS IVA and 11 children with MPS VI, observed no significant effect of upper airway surgery on the frequency and severity of sleep apnea [ 117 ]. While adenotonsillectomy and CPAP are used only to relieve upper airway obstruction—as poor effects on the progressively deteriorating course were demonstrated—ERT and HSCT, targeting the metabolic disorder, could successfully impact the severity of OSAS.…”

“…CSA can also occur in MPS patients due to several factors, including spinal cord cervico–occipital compression and dysfunction of brainstem’s sleep regulatory mechanism caused by GAG deposition in the central nervous system and increased intracranial pressure [ 118 ]. However, CSA is not well described and data on prevalence and impact are not yet defined [ 117 ]. These data highlight the importance of extending screening approaches, already present for more common syndromes such as DS, in MPS disorders, in which risk of experiencing SDB is even greater [ 122 ].…”