Pompe disease

Pompe disease: a debilitating, rare disease

Pompe disease is a rare, autosomal recessive inherited disease, in which mutations in the GAA gene lead to absent or reduced levels of the lysosomal enzyme acid alpha-glucosidase. Deficient activity of this enzyme leads to accumulation of glycogen, primarily in muscle tissue. The clinical presentation of Pompe disease typically involves weakness in cardiac and skeletal muscle^1-5.

Pompe disease is classified as early (infantile; IOPD) or late-onset (LOPD)^6,7. IOPD presents with severe cardiac dysfunction (e.g., hypertrophic cardiomyopathy) and respiratory insufficiency, and is commonly lethal within 1 year of age without treatment. LOPD typically presents with a pattern of symmetric limb-girdle muscle weakness. LOPD can manifest at any age after 1 year^1-5.

Best-practice management of Pompe disease is multidisciplinary, and involves early identification (e.g., newborn screening), blood sampling, symptomatic care, assessing for complications, and disease-modifying treatments, such as enzyme replacement therapy^1-5. Current treatments for the disease have significant unmet needs⁴.

Unmet needs in Pompe disease

Being a rare disease, there are numerous unmet needs in the clinical management of Pompe disease, many requiring a multidisciplinary strategy. Some of these include:

• The clinical and socioeconomical burden of Pompe disease
• The need for early Pompe disease diagnosis, awareness of its signs, symptoms and common misdiagnoses, and multidisciplinary strategies for diagnostic confirmation
• Optimising treatments of Pompe disease, including enzyme replacement therapy
• The importance of multidisciplinary disease monitoring over time

References

1. Tarnopolsky M, Katzberg H, Petrof BJ, Sirrsm S, Sarnat HB, Myers K, et al. Pompe disease: diagnosis and management. Evidence-based guidelines from a Canadian expert panel. Can J Neurol Sci. 2016;43(4):472–485.
2. Barba-Romero MA, Barrot E, Bautista-Lorite J, Gutierrez-Rivas E, Illa I, Jimenez LM, et al. Clinical guidelines for late-onset Pompe disease. Rev Neurol. 2012;54(8):497–507.
3. Llerena Junior JC, Nascimento OJ, Oliveira ASB, Dourado Junior MET, Marrone CD, Siqueira HH, et al. Guidelines for the diagnosis, treatment and clinical monitoring of patients with juvenile and adult Pompe disease. Arq Neuropsiquiatr. 2015;74(2):166–176.
4. Stevens D, Milani-Nejad S, Mozaffar T. Pompe Disease: a Clinical, Diagnostic, and Therapeutic Overview. Curr Treat Opt Neurol. 2022;24:573–588.
5. Morales A, Anilkumar AC. Glycogen Storage Disease Type II. StatPearls: Treasure Island (FL): StatPearls Publishing; 2023.
6. Engel AG. Acid maltase deficiency of adult life. Trans Am Neurol Assoc. 1969;94:250–252.
7. Engel AG. Acid maltase deficiency in adults: studies in four cases of a syndrome which may mimic muscular dystrophy or other myopathies. Brain. 1970;93(3):599–616.