Sleep Breath DOI 10.1007/s11325-014-0944-6

ORIGINAL ARTICLE

Prevalence of obstructive sleep apnea in patients with mucopolysaccharidosis types I, II, and VI in a reference center Gustavo A. Moreira & Sandra O. Kyosen & Camilla L. Patti & Ana Maria Martins & Sergio Tufik

Received: 23 September 2013 / Revised: 29 November 2013 / Accepted: 21 January 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract Purpose Mucopolysaccharidosis (MPS) encompasses a group of rare lysosomal storage disorders that are associated with the accumulation of glycosaminoglycans in organs and tissues. Respiratory disorders occur in all MPS types. In these patients, the prevalence of obstructive sleep apnea syndrome (OSAS), which may confer additional morbidity, remains overlooked, and the results of the few existing studies are controversial. The present study aimed to characterize the prevalence of OSAS in patients with MPS types I, II, and VI in a reference center. Methods Forty-five patients with MPS (I, n=17; II, n=16; and VI; n=12) in the Centro de Referência em Erros Inatos do Metabolismo, who underwent full-night polysomnography, were enrolled in a retrospective study. Demographic data and clinical history were collected from medical records of the first medical consultation. Results The prevalence of OSAS in patients with MPS was 69.8 %. MPS type I patients seemed to be more susceptible to OSA-induced hypoxemia, as indicated by reduced mean SpO2 levels during both NREM and rapid eye movement sleep as well as during SpO2 nadir. Conclusions Patients with MPS displayed a high prevalence of OSAS, often with moderate to high severity. Together, our G. A. Moreira (*) Instituto do Sono, Rua Marselhesa, 500, 14º andar, 04020-060 São Paulo, Brazil e-mail: [email protected] S. O. Kyosen : C. L. Patti : A. M. Martins Centro de em Erros Inatos do Metabolismo (CREIM), Universidade Federal de São Paulo, Rua Coronel Lisboa, 957, 04020-041 São Paulo, Brazil S. Tufik Departamento de Psicobiologia, Universidade Federal de São Paulo, Rua Napoleão de Barros, 925, São Paulo, SP, Brazil

results reinforce the need for OSAS screening in all patients with MPS. Keywords Lysosomal storage diseases . Inborn error of metabolism . Sleep-disordered breathing . Hypoxia . Polysomnography

Introduction Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders in which specific enzymes responsible for the catabolism of glycosaminoglycans are deficient [1]. The resulting accumulation of glycosaminoglycans leads to cell, tissue, and organ dysfunction [2]. Eleven known enzyme deficiencies underlie seven distinct MPS types (I, II, III, IV, VI, VII, and IX) [3]. Except for MPS type II (Hunter syndrome), which is inherited as an X-linked trait, all MPS types are transmitted as autosomal recessive disorders. The incidence of MPS is 1.9–4.5 in 100,000 live births [4], whereas the overall prevalence is 3.5–4.8 in 100,000 in Australia and some European countries [5, 6]. Respiratory disorders occur in all MPS types [7–11]. In fact, airway abnormalities, including airway obstruction during sleep, have been cited as one of the main causes of morbidity and mortality in patients with MPS [12]. Of note, the exact prevalence of sleep-disordered breathing in these patients is not known [10]. Obstructive sleep apnea syndrome (OSAS) is defined as a disorder of breathing during sleep characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction (obstructive apnea) that disrupts normal ventilation during sleep and normal sleep patterns. The syndrome is often accompanied by several characteristic symptoms or signs [13]; in children, snoring and disturbed sleep are the most common symptoms. OSAS leads to developmental delay, behavioral

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problems, failure to thrive, decreased quality of life, congestive heart failure, and pulmonary and systemic hypertension [14, 15]. Furthermore, OSAS can contribute to additional neurocognitive morbidity [16]. Due to its adverse impact, screening for OSAS is strongly recommended in MPS patients [17]. The estimated OSAS prevalence in patients with MPS is at least 40 %, four times greater than that of the general population [18]. However, there is a paucity of literature on this issue, and data from the few existing studies are controversial. Progressive compromise of the upper airways is extremely frequent in patients with MPS types I, II, and VI [3, 19]. Therefore, OSAS may result in premature death [3, 8, 19]. Within this context, we aimed to characterize the prevalence of OSAS in patients with MPS types I, II, and VI in a reference center.

Methods Subjects Forty-five patients with MPS (MPS I, n=17; MPS II, n=16; and MPS VI; n=12) in the Centro de Referência em Erros Inatos do Metabolismo (CREIM) of Universidade Federal de São Paulo (UNIFESP) were enrolled in the study. No patients were treated with enzyme replacement therapy or any respiratory devices during the study. The study was approved by local Institutional Review Boards/the Ethics Committee of the UNIFESP under the protocol #2007/11. Data handling A retrospective study was conducted using data from the medical charts of MPS patients as well as data from the initial polysomnography, which was conducted in the Instituto do Sono, São Paulo. The medical consultations occurred between May 1997 and May 2011, and the polysomnographies (PSG) were performed between September 1998 and August 2010. Diagnosis of MPS was based on a deficiency in the activity of specific enzymes in serum, plasma, or leukocytes. Demographic data and clinical history, including age, height, weight, comorbid medical conditions, cardinal clinical signs of MPS and previous airway surgery, were obtained from the clinical records of the first medical consultation. Body mass index (BMI) z scores were calculated using Anthros or AnthrosPlus from the World Health Organization Child Growth Standards (http://www.who.int/childgrowth/ software/en/ and http://www.who.int/growthref/tools/en/).

treatment or enzyme replacement therapy. PSG was performed by trained professionals using the EMBLA (EMBLA® S7000, Inc., Broomfield, CO, USA) or the Alice Host (Philips/Respironics®, Marieta, GA, USA) systems. Biological variables were measured with electroencephalography (C3/A2, C4/A1, O1/A2, O2/A1), electrooculography, submental and anterior tibial electromyography, and electrocardiography (V2 modified). Airflow was measured through an oronasal thermistor and a nasal cannula with a pressure transducer. Thoracic and abdominal movements were monitored with piezoelectric transducers, snoring was recorded using a microphone, oxygen saturation and the pulse plethysmographic wave form were measured using pulse oximetry, and body position was monitored by a sensor. Sleep scoring was performed by a trained PSG technician and was based on the criteria set forth by Rechtschaffen and Kales [20]. Respiratory events and arousals were analyzed according to international criteria [21, 22]. Briefly, an arousal was defined as an abrupt shift in electroencephalogram (EEG) signals to alpha frequencies (8–13 Hz) or frequencies >16 Hz for a minimum of 3 s. During rapid eye movement (REM) sleep, arousals were scored if the change in EEG frequency was accompanied by a concomitant increase in the amplitude of the submental electromyogram (EMG) signal. Obstructive apneas were defined as the presence of chest and/or abdominal motion in the absence of airflow. As children have a higher respiratory frequency than adults and frequently desaturate even with short apneas, all obstructive apneas greater than or equal to two breaths in duration were counted. Hypopneas were defined as a qualitative decrease in the oronasal airflow ≥50 % associated with paradoxical chest wall motion and oxygen desaturation ≥3 %. The apnea-hypopnea index (AHI) was defined as the number of obstructive apneas, mixed apneas, and hypopneas per hour of sleep. The obstructive apnea index (OAI) was defined as the number of obstructive apneas and mixed apneas per hour of sleep. The awake baseline oxygen saturation (SpO2), SpO2 nadir, and mean SpO2 during REM and NREM were determined. SpO2 measurements associated with a poor pulse waveform were discounted. As OSAS in children differs from that in adults, age-specific criteria were used for diagnosis. Primary snoring was defined as a history of snoring, recording of snoring during PSG, an obstructive apnea index ≤1/h, an apneahypopnea index ≤1.5, and SpO2 nadir ≥92 %. OSAS criteria was defined by an obstructive apnea index >1/h or an apneahypopnea index >1.5/h associated with oxygen desaturation

Prevalence of obstructive sleep apnea in patients with mucopolysaccharidosis types I, II, and VI in a reference center.

Mucopolysaccharidosis (MPS) encompasses a group of rare lysosomal storage disorders that are associated with the accumulation of glycosaminoglycans in...
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