Rate of progression and predictive factors for pulmonary outcome in children and adults with Pompe disease
Introduction
Pompe disease is a rare inherited metabolic disorder [1], [2], [3], [4] caused by deficiency of the lysosomal enzyme acid α-glucosidase. The spectrum of phenotypes is continuous, but in clinical practice two subtypes can be recognized: 1) the classic infantile phenotype, in which the disease manifests shortly after birth, leading to generalized muscle weakness, cardiorespiratory failure and death within the first year of life [5], [6]; and 2) a more slowly progressive phenotype predominantly affecting skeletal and respiratory muscles, in which cardiac involvement is only sporadically present [7], [8]. Symptoms in this latter group of patients can become manifest at any age, from as early as the first year of life to as late as the sixth decade [9], [10], [11], [12]. The course of the disease can vary substantially between patients [13], and the severity of respiratory involvement is not always related to the degree of skeletal–muscle weakness [14], [15].
Due to the disproportionate involvement of the diaphragm, respiratory insufficiency is a serious threat to patients with Pompe disease [16], [17]; this is also seen in several other neuromuscular disorders such as Duchenne muscular dystrophy or facioscapulohumeral dystrophy. As the disease progresses, many patients ultimately become dependent on mechanical ventilatory support, and respiratory failure is a major cause of death [7], [12]. However, most studies have investigated only a small number of patients, or only a selected group; the actual percentage of patients with respiratory dysfunction, who are thus at risk for developing respiratory failure, is therefore not exactly known [11], [14], [15], [17]. Neither is it known which factors are associated with poor pulmonary outcome.
In April 2010, a placebo controlled trial showed that pulmonary function in patients older than eight years may be stabilized by treatment with recombinant human alpha-glucosidase. Early identification of respiratory problems may thus be important for the timely initiation not only of mechanical ventilation, but also of enzyme therapy [18], [19].
To establish the proportion of patients with pulmonary involvement, and also the severity of pulmonary dysfunction and the rate of deterioration, we conducted a prospective cohort study in 92 untreated children and adults with Pompe disease. We also aimed to identify predictive factors for poor respiratory outcome.
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Study population and study design
Ninety-two patients (17 children and 75 adults) were included in an ongoing prospective cohort study on the natural course of Pompe disease. Participation was open to all patients who did not have the classic infantile type of Pompe disease. Diagnosis in all patients was confirmed through mutation analysis and by measuring acid alpha-glucosidase deficiency in leukocytes, muscle tissue or fibroblasts.
All patients were examined at Erasmus MC University Medical Centre between August 2003 and
Clinical characteristics
The study population comprised 92 patients with Pompe disease: 17 children aged between 5 and 17 years, and 75 adults. Fifty-four percent of the patients were male. Disease duration at the time of the initial investigation ranged from 0 to 47 years. The median age at which patients had experienced their first symptoms was 30 years (range 1 to 62 years). Seven patients (six children and one adult) had been diagnosed within the first two years of life. None of these patients had a hypertrophic
Discussion
The purposes of our study were to determine the proportion and severity of pulmonary involvement in patients with Pompe disease, the rate of deterioration of pulmonary function, and to identify predictive factors for poor respiratory outcome.
With regard to the proportion of patients with pulmonary involvement, we found that 79% of the adults and 59% of the children, had some degree of pulmonary dysfunction.
With regard to severity, 42 patients, 26 of whom used mechanical ventilation, had a
Acknowledgments
The authors thank all patients for participating in the study, all physicians for referral of the patients, and David Alexander for his critical reading of the manuscript. Research on Pompe disease at Erasmus MC is financially supported by the Erasmus MC Revolving Fund [project number 1054, NAMEvdB]; European Union, 7th Framework Programme “Euclyd — a European Consortium for Lysosomal Storage Diseases” [health F2/2008 grant number 201678]; ZonMw — Netherlands organization for health research
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2020, Neuromuscular DisordersCitation Excerpt :MIP and MEP are recommended as an additional standard diagnostic assessment in NMDs as they may detect respiratory insufficiency earlier than FVC and show a high association with early mortality [9–11]. As a result of this, assessments of respiratory muscle strength have been broadly used in longitudinal studies on the decline of RMW in amyotrophic lateral sclerosis, Duchenne muscular dystrophy and Pompe disease [2,3,12,13]. They serve as clinically meaningful outcome measures in various clinical trials [14].