Disordered breathing during sleep in patients with mucopolysaccharidoses

Abstract

Objective: Obstructive sleep apnoea (OSA) has been reported as a feature of children with mucopolysaccharidoses (MPS). However, the incidence and severity of OSA with respect to disease type is poorly defined. The aim of the present study was to measure objectively the degree of OSA in a group of children with a range of MPS syndromes. Methods: In a cross-sectional study, cardiopulmonary sleep studies were performed during unsedated sleep in 26 children with MPS over a period of 2 years. Scores of OSA severity based upon clinical history and upon objective sleep study data were made in each case and compared. Results: OSA was present in 24/26 patients, and ranged in severity from mild to severe. OSA was most marked in MPS type IH (Hurler syndrome) followed by types IHS (Hurler–Scheie syndrome) and II (Hunter syndrome). Frequent arousals and poor sleep quality, not suspected clinically, were noted in several patients. There was agreement between the clinical and objective scoring systems in only 17/26 patients (65%) with clinical history scores tending to underestimate the most severe cases (5/26 cases) and overestimate the severity in the mild cases (4/26 cases). Conclusions: Obstructive respiratory problems are frequent in MPS patients and there are differences in severity of OSA between the different MPS types. Assessments of the severity of OSA based upon clinical history alone are inadequate. Our results suggest that objective sleep studies are necessary to evaluate these cases, to monitor clinical outcome and to assess the effects of therapeutic intervention. Prospective studies in larger numbers of patients are needed to validate these observations.

Introduction

The mucopolysaccharidoses (MPS) are a group of genetic disorders, classified biochemically by defective lysosomal catabolism of glycosaminoglycans [1] and leading to an accumulation of specific glycosaminoglycans (Table 1). Respiratory involvement is common in affected individuals, and is progressive, with the precise timing, nature and severity related to the underlying disorder [2]. Affected individuals classically have a number of anatomical features predisposing them to airway compromise [2], [3]. In the upper airway these include abnormal cervical vertebrae, a short neck, a high epiglottis, a deep cervical fossa narrowing the nasopharynx and a hypoplastic mandible with short rami [3]. In the lower airway there is a small thoracic cage, frequently complicated by kyphoscoliosis. In addition, glycosaminoglycans are progressively deposited in the tissues surrounding the upper respiratory tract in the nasopharynx, oropharynx, hypopharynx and larynx, and this may contribute to upper airway obstruction (UAO) [2]. Tonsillar [4] and adenoidal [5] hypertrophy and macroglossia [3], [6] are recognised features and there is progressive distal spread of airway obstruction as tracheobronchial cartilage is affected and tracheobronchial narrowing and tracheobronchomalacia ensue [7], [8]. Furthermore, hepatosplenomegaly may limit diaphragmatic excursion, and interstitial pulmonary deposition of mucopolysaccharides may result in a diffusion defect. Thickened and copious secretions throughout the upper and lower respiratory tracts are also commonly found and there is a tendency to frequent upper and lower respiratory tract infections [9], [10]. Chronic hypoxaemia may result in pulmonary hypertension, and cor pulmonale [2]; cardiorespiratory failure is the usual cause of death. Breathing may only be significantly obstructed when affected individuals are sleeping [2]. During active (rapid eye movement, REM) sleep, the upper airway is vulnerable to collapse, as there is a physiological decrease in tone of the supporting muscles and consequent increase in resistance to airflow [11]. When this is superimposed on an already narrow airway, obstruction may develop and breathing may become impaired, resulting in obstructive sleep apnoea (OSA).

The aim of the present study was to evaluate and document the breathing patterns during sleep of untreated children with MPS. It was anticipated that the availability of baseline data for breathing patterns in these children would facilitate the diagnosis and quantification of the severity of UAO. Furthermore objective scoring systems will assist in the evaluation of the effect on the airway of therapeutic interventions such as adenotonsillectomy, tracheostomy, nasal continuous positive airways pressure (n-CPAP) or bone marrow transplantation.

Our criteria for assessment of respiration during sleep based on clinical history and observation are also reported, and the relationship of the results of such clinical assessments with those of objective sleep study results examined. If good correlation can be achieved, it may reduce the frequency of need for serial sleep studies in the management of children with MPS and obstructive airway disorders.