Pompe Disease (PD)

Patients with Pompe disease inherit biallelic mutations in the acid alpha-glucosidase (GAA) gene, located on chromosome 17q25. These cause a deficiency of the lysosomal enzyme GAA. The severity of the condition depends on the level of residual enzymatic activity. GAA activity is less than 1% of normal in classic infantile-onset Pompe disease (IOPD). Unlike late-onset forms of Pompe disease, in which the clinical presentation is milder, IOPD is characterized by glycogen deposition in skeletal muscle, the heart, and other tissues. During the first 6 months of life, elevated creatinine kinase, hypertrophic cardiomyopathy, failure to thrive, muscle hypotonia, and axial muscle weakness develop in affected infants.¹ Read about how the disease may affect life expectancy.

Life Expectancy in Classic Infantile-Onset Pompe Disease

If timely therapy is not available for individuals with an early-onset (classic, infantile) form of Pompe disease, the course will be severe and is likely to result in death. Respiratory weakness, which presents at various ages in late-onset disease, is a frequent cause of death in both early- and late-onset disease. Cardiomegaly with progressive blockage of left ventricular outflow is another frequent cause of mortality in IOPD.² Pneumonia is likely to occur in patients with weak respiratory muscles and swallowing difficulties.³ Most children with untreated IOPD die during the first year of life of a combination of ventilatory and cardiac failure before reaching motor milestones such as sitting, turning, and standing. It is rare for an affected child to live past the age of 18 months.¹ 

Life Expectancy in Nonclassic Infantile-Onset Pompe Disease

The nonclassic variant of infantile-onset Pompe disease is less severe. It manifests in the first year of life and progresses more slowly than the classic variant, but heart disease and respiratory difficulties frequently develop that can be lethal if not treated promptly.⁴ Nonclassic (late-infantile) Pompe disease, which appears in infancy but in which cardiac hypertrophy is absent or mild, must be differentiated from classic IOPD.¹

Life Expectancy in Late-Onset Pompe Disease

Late-onset Pompe disease (LOPD) may be seen at any age. The concentration of the acid alpha-glucosidase enzyme is higher in patients with this type than in people with more severe disease. Patients with LOPD experience muscle weakness and respiratory difficulties. If the condition starts in childhood, patients may survive up to the age of 30 years; if it starts in adulthood, they can live to 50 years of age. In general, the later the onset of disease, the slower its progression and the longer the patient’s life expectancy.⁴ Peripheral muscle weakness and respiratory muscle weakness, which are symptoms of the adult form of the disease, can carry a poor prognosis and shorten life expectancy. Aneurysms may develop in the brain if glycogen accumulates in the blood vessels.³

Life expectancy depends on when the disease first appears and the speed at which the symptoms worsen. Symptoms such as difficulty walking and climbing stairs start slowly and worsen with time. People with LOPD, like those with early-onset disease, may experience respiratory difficulties. As the disease progresses, they may eventually become wheelchair-dependent or bedridden and require a respirator.⁵ Even though Pompe disease has no cure, if it is detected early, the symptoms can be controlled and patients’ lives extended. The first line of treatment is enzyme replacement therapy (ERT); Lumizyme (alglucosidase alfa) should be started as soon as the diagnosis is confirmed. Support therapy, in addition to ERT, can improve patients’ quality of life. Physical, occupational, and speech therapy can enhance muscular strength and facilitate the intake of food. To alleviate eating problems caused by weak muscles of swallowing, dietary adjustments may be required. In general, a high-protein, low-carbohydrate diet is advised. Problems with respiratory muscles are also common; therefore, it is critical to identify breathing issues early with pulmonary function testing and address them. The use of equipment to assist breathing, such as mechanical ventilators, may be necessary.⁴ 

References 

1. Hahn A, Schänzer A. Long-term outcome and unmet needs in infantile-onset Pompe disease. Ann Transl Med. 2019;7(13):283. doi:10.21037/atm.2019.04.70
2. Morales JA, Anilkumar AC. Glycogen storage disease type II. StatPearls [Internet]. Published August 11, 2021. Accessed March 3, 2022.
3. Cunha JP. What is the life expectancy of someone with Pompe disease? eMedicineHealth. Reviewed June 26, 2020. Accessed March 3, 2022.
4. Subramaniam V. How does Pompe disease affect life expectancy? Pompe Disease News. Published October 28, 2019. Accessed March 3, 2022.
5. Kugler M. Pompe’s disease symptoms and treatments. VerywellHealth. Updated September 20, 2021. Accessed March 3, 2022.

Reviewed by Hasan Avcu, MD, on 3/19/2022.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.