Upper airway obstructive disease in mucopolysaccharidoses: polysomnography, computed tomography and nasal endoscopy findings.
ABSTRACT In mucopolysaccharidoses, upper airway obstruction has multiple causative factors and progressive respiratory disease may severely affect morbidity and mortality. In a cross-sectional study over 2 years we evaluated upper airway obstructive disease through overnight polysomnography, upper airway computed tomography and nasal endoscopy in 5 children and 6 adults with mucopolysaccharidoses of various types. Measurements of apnoea and apnoea-hypopnoea index, arousal index, and sleep efficiency were obtained through polysomnography. Retropalatal and retroglossal spaces were calculated through computed tomography, and the degree of adenoid hypertrophy was assessed through endoscopy. Apnoea index and apnoea-hypopnoea index were significantly higher in children than in adults with mucopolysaccharidoses (p = 0.03 and p = 0.03, respectively). Compared to healthy controls, retropalatal and retroglossal spaces were significantly smaller in children (p = 0.03 and p = 0.004, respectively) or adults with mucopolysaccharidoses (p = 0.004 and p = 0.004, respectively). All subjects had adenoid hypertrophy causing first-degree (36%) or second-degree (64%) obstruction at endoscopy. Overnight polysomnography, upper airway computed tomography and nasal endoscopy are useful tools for diagnosing obstructive sleep apnoea syndrome in mucopolysaccharidoses, and identifying the site and severity of airway obstruction.
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ABSTRACT: The mucopolysaccharidoses (MPS), a group of rare genetic disorders caused by defects in glycosaminoglycan (GAG) catabolism, are progressive, multi-systemic diseases with a high burden of morbidity. Enzyme replacement therapy (ERT) is available for MPS I, II, and VI, and can improve walking ability, endurance, and pulmonary function as evidenced by data from pivotal trials and extension studies. Despite these demonstrable benefits, cardiac valve disease, joint disease, and skeletal disease, all of which cause significant morbidity, do not generally improve with ERT if pathological changes are already established. Airway disease improves, but usually does not normalize. These limitations can be well understood by considering the varied functions of GAG in the body. Disruption of GAG catabolism has far-reaching effects due to the triggering of secondary pathogenic cascades. It appears that many of the consequences of these secondary pathogenic events, while they may improve on treatment, cannot be fully corrected even with long-term exposure to enzyme, thereby supporting the treatment of patients with MPS before the onset of clinical disease. This review examines the data from clinical trials and other studies in human patients to explore the limits of ERT as currently used, then discusses the pathophysiology, fetal tissue studies, animal studies, and sibling reports to explore the question of how early to treat an MPS patient with a firm diagnosis. The review is followed by an expert opinion on the rationale for and the benefits of early treatment.Molecular Genetics and Metabolism 01/2013; · 2.83 Impact Factor
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ABSTRACT: Upper airway obstruction is common in children with mucopolysaccharidosis. The acoustic reflection method is a noninvasive technique that can analyze the caliber of the upper airways. The aim of the study was to evaluate the feasibility of the acoustic reflection method in children with mucopolysaccharidosis, and to compare the characteristics of the upper airways evaluated by the acoustic reflection method in patients with mucopolysaccharidosis to matched healthy counterparts. Open, single center, prospective, study. Accurate acoustic reflection measurements could be obtained in 7 of 10 patients (mean age: 10.4 ± 3.9 years; mucopolysaccharidosis type II (n = 3); type IV (n = 2), type VI (n = 1), and fucosidosis (n = 1)). The mean minimum cross-sectional area was lower in mucopolysaccharidosis patients (1.6 ± 0.3 cm(2) ) as compared to 14 healthy counterparts (1.8 ± 0.3 cm(2); P = 0.03). The mean resistance of the airways was significantly higher in the MPS group (7.9 ± 1.8 cmH(2) O l(-1) sec) as compared to the controls (5.5 ± 1.2 cmH(2) O l(-1) sec; P = 0.006). This study is the first to analyze the upper airways by the noninvasive acoustic reflection method in children with mucopolysaccharidosis. Due to a lack of cooperation, reliable measurements could only be obtained in 70% of a selected group of patients. Children with mucopolysaccharidosis have significant upper airway obstruction as assessed by the reduction of the minimal cross-sectional area of the upper airways and the increase in airway resistance.Pediatric Pulmonology 01/2011; 46(6):587-94. · 2.38 Impact Factor
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ABSTRACT: BACKGROUND: Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by the deficiency of hydrolases involved in the degradative pathway of glycosaminoglycans. In MPS, upper airway obstruction may result from multiple causative factors which may impact severely upon morbidity and mortality. METHODS: We evaluated upper airway obstructive disease and related clinical findings through home sleep study in 19 patients (11 with MPS VI, 4 with MPS I, 4 with MPS II) with MPS followed at Gazi University Pediatric Metabolic Unit. Patients underwent home-based sleep measurements, and sleep respiratory problems were asked in a detailed clinical history. Measurements of apnea, apnea-hypopnea index (AHI), hypopnea index, oxygen desaturation index, and minimal oxygen saturation were obtained through home sleep study. RESULTS: For 19 children, the disorder was normal in 1, mild (AHI = 1.5-5/h) in 5, moderate (AHI = 5-10/h) in 2, and severe (AHI > 10/h) in 11. The prevalence of OSA was 94.7 % (18/19) in patients with MPS. Snoring, witnessed apnea, pectus carinatum, and macroglossia were the main clinical findings. Echocardiograms showed evidence of pulmonary hypertension in 13 patients. CONCLUSION: Home sleep study is a quick and accessible screening test to determine the abnormalities of breathing during sleep and enables clinicians to take necessary action for patients with severe manifestations.Sleep And Breathing 05/2013; · 2.26 Impact Factor