Elsevier

Neuromuscular Disorders

Volume 19, Issue 2, February 2009, Pages 113-117
Neuromuscular Disorders

Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease

https://doi.org/10.1016/j.nmd.2008.11.007Get rights and content

Abstract

To determine the rate of disease progression in patients with late-onset Pompe disease, we collected longitudinal data on pulmonary function and skeletal muscle strength in 16 patients whose symptoms had started in childhood or adulthood. The mean duration of follow-up was 16 years (range 4–29 years). During the follow-up period, eight patients (50%) became wheelchair bound and three (19%) became ventilator dependent. At a group level, pulmonary function deteriorated by 1.6% per year, and proximal muscle weakness progressed gradually. At the individual level, however, the rate and extent of progression varied highly between patients. In two thirds of patients, pulmonary function and muscle strength declined simultaneously and to the same extent. The remaining one third of patients showed a variable, sometimes rapidly progressive course, leading to early respirator or wheelchair dependency. These individual differences, especially in pulmonary dysfunction, indicate the need for regular monitoring every 6–12 months depending on the rate of disease progression.

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.

Section snippets

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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