Pompe Disease: Late Onset

The late-onset form of Pompe disease can present anytime during early childhood up until adulthood with a diffuse array of manifestations. In many cases, the first observations may be difficulty walking or climbing stairs and gradually progressive proximal muscle weakness, simulating the symptoms of Duchenne or limb-girdle muscular dystrophy. In other cases, respiratory symptoms may surface prior to any recognition of muscle weakness.

In children, the disease may present with delayed motor milestones but intelligence is generally normal. As in the infantile-onset form, there is generally hypotonia and eventual respiratory distress. Macroglossia and hepatomegaly may be present in some cases, but there is rarely any cardiac involvement^[1]. The degeneration of skeletal muscle may also result in lumbar lordosis and/or scoliosis, which can occasionally require surgical correction. Some patients display an unsteady gait and, occasionally, toe walking.

Progressive proximal muscle weakness, especially in the trunk

Progressive muscle weakness in the lower limbs

Respiratory insufficiency

Exercise intolerance

Exertional dyspnea

Orthopnea

Sleep apnea

Morning headaches

Somnolence

Lordosis and/or scoliosis

Hypotonia

Hepatomegaly

Macroglossia (uncommon)

Difficulty chewing and swallowing

Increased frequency of respiratory infections

Decreased deep tendon reflexes

Gower sign

Lower back pain

Failure to meet motor milestones (children)

Adults also present with progressive myopathy, primarily in the trunk and lower limbs. Not all areas may be affected equally, however, and there have been reports of distal muscle weakness and scapular winging^[5]. A key clinical feature that may help to distinguish late-onset Pompe disease from other neuromuscular disorders is the early involvement of the respiratory muscles. However, not all patients with late-onset Pompe disease develop respiratory muscle symptoms. As respiratory insufficiency advances, patients may experience morning headaches, orthopnea, exertional dyspnea, sleep apnea, somnolence, and/or exercise intolerance. In some cases the Gower sign may be present.

Respiratory muscle weakness typically serves as the most debilitating and lethal feature of late-onset Pompe disease. A 2001 study that evaluated 27 juvenile and adult patients found that 17 of 27 subjects experienced ventilatory restriction, and 13 of 27 patients showed diaphragm weakness. Of those 13 patients, 12 suffered from sleep disordered breathing, including REM-sleep hypopnea and hypoventilation. The authors confirmed the assumption that diaphragm weakness is a major cause of sleep disordered breathing and respiratory failure, and also concluded that vital capacity correlates with respiratory muscle function.^[6]

The disease course for late-onset Pompe disease varies widely, making morbidity and life expectancy difficult to predict. Some patients with less severe symptoms remain functional with only minimal disability for years, while others eventually require ventilator support and an orthosis or wheelchair. Ventilator support and tracheostomy may improve quality of life and extend survival in those with severe respiratory impairment, but death usually results from respiratory failure^[1] Those who present as juveniles generally live into the third decade,^[1] while those who present later can demonstrate a greater range of outcomes.

1. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid Alpha-Glucosidase (Acid Maltase) Deficiency. In: Wonsiewicz M, Noujaim S, Boyle P, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill; 2001; 3389-3420.

2. King, Frank J. Acid Maltase Deficiency Myopathy. eMedicine Specialties. Available at: http://www.emedicine.com/pmr/topic2.htm . Accessed November 7, 2002.

3. Ibrahim, Jennifer. Glycogen Storage Disease Type II. eMedicine Specialties. Available at: http://www.emedicine.com/ped/topic1866.htm Accessed November 7, 2002.

4. Personal communication with Jennifer Hofstein, MS, RD, and Alfred Slonim, MD, at North Shore University Hospital Pediatric Endocrinology & Metabolism, Manhasset, New York.

5. Felice KJ, Alessi AG, and Grunnet ML. Clinical variability in adult-onset acid maltase deficiency: report of affected sibs and review of the literature. Medicine 1995 May; 74(3): 131-5.

6. Mellies U, Ragette R, Schwake C, et al. Sleep-disordered breathing and respiratory failure in acid maltase deficiency. Neurology 2001 Oct 9; 57(7): 1290-5.



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