INTRODUCTION

Pompe disease—also known as acid maltase deficiency, glycogen storage disease type II, and glycogenosis type II—is a metabolic myopathy caused by a deficiency of lysosomal acid α-glucosidase (GAA), an enzyme needed to break down glycogen. The resulting glycogen accumulation causes progressive damage to the skeletal, respiratory, and cardiac muscle, which leads to functional impairment, irreversible damage to muscle tissue, permanent disability, and often early death. The Pompe disease continuum ranges from a rapidly progressive course that is usually fatal by 1 year of age to a more variable and relentlessly progressive course with significant morbidity and/or premature mortality.

Infantile-onset Pompe disease presents with hypertrophic cardiomyopathy, muscle weakness, and hypotonia; most of these infants die by 1 year of age from cardiorespiratory failure. A retrospective study of the natural history of infantile-onset Pompe disease showed that the median age at symptom onset was 2.0 months, median age at diagnosis was 4.7 months, median age at first ventilator support was 5.9 months, and median age at death was 8.7 months.¹ Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA, alfa glucosidase, Myozyme^®, Genzyme Corporation) in 18 infants <6 months of age reduced the risk of death by 99%, risk of death or invasive ventilation by 92%, and risk of death or any type of ventilation by 88%,² compared with an untreated reference cohort.¹ Earlier initiation of therapy may be associated with improved clinical outcomes.

Pompe disease in children and adults presents with progressive muscle weakness leading to wheelchair and ventilator dependence and often premature death from respiratory failure. While most children and adults with Pompe disease present with proximal limb-girdle muscle weakness, especially in the lower body, a small proportion of patients experience respiratory insufficiency before muscle weakness.³

The natural history of Pompe disease in children and adults, including severity and rate of progression, can be extremely variable. A survey of 225 children and adults with Pompe disease showed that disease severity is related to duration of disease symptoms, not to the age of the patients.⁴ With each additional year following diagnosis, wheelchair use increased by 13% and odds for respiratory support increased by 8%. In a case series of 16 untreated Dutch patients aged 4 to 29 years who were followed for a mean duration of 16 years, 8 patients (50%) became wheelchair dependent and 3 patients (19%) became ventilator dependent.⁵ Approximately two-thirds of these patients showed parallel decline in skeletal muscle strength and pulmonary function, while one-third had a more variable, and in some cases extremely rapid, disease course.

Because Pompe disease can be so variable, and because the disease shares symptoms with other, more common conditions, diagnostic delay can often result. In 38 children and adults with Pompe disease, the mean delay from symptom onset or first medical consultation to diagnosis was 10.4 and 7.1 years, respectively.⁶ Eleven of these patients were initially diagnosed with a different condition and ten patients underwent multiple muscle biopsies before the correct diagnosis of Pompe was made.

A recent randomized, controlled trial in 90 children and adults with Pompe disease found that patients receiving enzyme replacement therapy had a favorable effect compared to placebo. In this study population, treatment with alglucosidase alfa resulted in improved walking distance and stabilization of pulmonary function over an 18-month period.⁷

Pompe disease is inherited as an autosomal recessive disorder. If both parents have one copy of a Pompe disease-causing gene, there is a 25% chance with each pregnancy that the child will have the disease.

1. Kishnani PS, Hwu WL, Mandel H, et al. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr. 2006;148(5):671-6.
2. Kishnani PS, Corzo D, Nicolino M, et al. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007;68(2):99-109.
3. Mellies U, Lofaso F. Pompe disease: A neuromuscular disease with respiratory muscle involvement. Respir Med. 2009. [epub ahead of print]
4. Hagemans ML, Winkel LP, Hop WC, et al. Disease severity in children and adults with Pompe disease related to age and disease duration. Neurology. 2005;64(12):2139-41.
5. Van der Beek NA, Hagemans ML, Reuser AJ, et al.  Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease. Neuromuscul Disord. 2008. [epub ahead of print]
6. Muller-Felber W, Horvath R, Gempel K, et al. Late onset Pompe disease: clinical and neurophysiological spectrum of 38 patients including long-term follow-up in 18 patients. Neuromuscul Disord. 2007;17(9-10):698-706.
7. van der Ploeg A, Becker A, Clemens P, et al. Results from a randomized, double-blind, multicenter, multinational, placebo-controlled study of the safety and efficacy of Myozyme, recombinant human acid alpha-glucosidase (rhGAA), for the treatment of Pompe disease in juvelines and adults. Presented at the 2008 Annual Meeting of the American Academy of Neurology.