Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease
Introduction
Pompe disease (glycogen storage disease type II or acid maltase deficiency) is characterized by intra-lysosomal glycogen storage caused by acid α-glucosidase deficiency. The estimated frequency of the disease is 1 in 40,000 newborns [1], [2], [3]. The clinical spectrum is broad, and disease severity is related primarily to the degree of enzyme deficiency. Patients with the classic infantile phenotype manifest generalized muscle weakness and a hypertrophic cardiomyopathy shortly after birth, and usually die within the first year of life due to cardiorespiratory failure [4], [5]. Patients with milder phenotypes usually present in the first to sixth decade of life with a slowly progressive proximal myopathy or, occasionally, with respiratory failure [6], [7], [8].
Enzyme replacement therapy (ERT) with recombinant human α-glucosidase has recently been approved as long-term treatment. In infants with Pompe disease, treatment prolongs survival [9], [10], [11], [12], [13], [14]. Variable effects on respiratory function and muscle have been reported both in infantile patients and in severely affected patients with late-onset disease [10], [15]. The results obtained so far indicate that the effect on clinical outcome is better when treatment is started early in the course of the disease, before irreversible muscle damage has occurred. However, experience is still limited, especially in older children and adults. To optimize the effect of ERT and determine its long-term effects, accurate knowledge of the rate of disease progression in untreated patients is crucial.
As yet, there is little information available on the long-term clinical course in patients with late-onset Pompe disease [16], [17], [18], [19]. We therefore, assessed the rate of deterioration of pulmonary function and skeletal muscle strength through longitudinal clinical follow-up of a group of untreated patients.
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Patients and methods
Clinical data were obtained from medical records of 16 Dutch patients with late-onset Pompe disease from 13 families. All were diagnosed between 1975 and 2002 and seen regularly at the University Medical Center Utrecht (n = 8) or the Erasmus MC University Medical Center Rotterdam (n = 8). The diagnosis was confirmed in all patients through mutation analysis and measurement of acid α-glucosidase deficiency in leukocytes, muscle tissue or fibroblasts. All measurements of pulmonary function and muscle
Clinical characteristics
Sixteen patients with Pompe disease were followed for a prolonged period of time. Ten of these 16 patients were female. All patients were ambulant at the time of their first visit. One patient used artificial ventilation at night. The mean age at first symptoms was 24 ± 11 years (range 1–40 years) and at diagnosis 27 ± 12 years. Four patients were diagnosed before the age of 18 (age at diagnosis 8, 11, 15 and 15 years). One patient was diagnosed pre symptomatically after measurement of an elevated
Discussion
Late-onset Pompe disease is known as a slowly progressive myopathy with or without respiratory involvement. However, information about the rate of disease progression in untreated patients, evaluated by physical examination, is largely lacking. In this study we longitudinally assessed the rate of deterioration in pulmonary function and proximal muscle strength in a group of 16 affected patients.
At a group level, we found a decline in respiratory function of 1.6% per year and a gradual
Acknowledgements
The authors thank Tom de Vries Lentsch for layout of the figures.
This study was supported by the Erasmus MC revolving fund (Project No. 1054, N.A.M.E van der Beek).
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