Glycogen storage disease type II
Citation, DOI & article data
Glycogen storage disease type II, also known as Pompe disease or acid maltase deficiency disease, is an inherited lysosomal storage disorder characterized by abnormal glycogen accumulation within lysosomes. It is a multisystem disorder involving the heart, skeletal muscle and liver. It is caused by a deficiency of lysosomic acid α-1,4 glucosidase.
The overall incidence is 1 in 40,000. There are three major forms of Pompe disease:
- infantile-onset: manifests within a few months of birth; occurs in 1 in 138,000 live births
- non-classic infantile-onset: manifests by one year of age; occurs in 1 in 57,000 births
- late onset: manifests in early or late childhood, adolescence or adulthood
Almost equal cases of male and female patients have been reported in literature 1.
The presentation may include one or a few of the following:
- muscle weakness/hypotonia
- motor delay
- hypertrophic cardiomyopathy
- failure to thrive
- respiratory infections
Late-onset disease often manifests itself with proximal muscle weakness, which may be interpreted as clumsiness 2.
On muscle biopsy, vacuolation and effacement of muscle fibers caused by the replacement of myocyte structures by visibly-evident glycogen can be seen. In severe cases, autophagic involvement in the myocytes along with complete disruption of myofibril architecture is seen 3.
Ultrasound scanning of the skeletal muscles may reveal hypoechogenicity of the skeletal muscles compared to the epimysium. The perimysium may also appear indistinct from the muscle 4.
CT may be the initial investigation, especially if performed for other reasons. Like MRI, it may reveal the characteristic pattern of fatty infiltration in a fairly symmetric manner and out of proportion to the patient's age but with apparent preservation of the muscle volume.
T2 weighted MRI reveals fatty infiltration of the tongue, muscles of respiration, paraspinal muscles, lateral abdominal muscles, latissimus dorsi and gluteal muscles. These findings correlated with symptoms experienced by patients. Of note, the severity of infiltration correlates with severity of disease and can predict prognosis 6. MRI appearances of skeletal muscle can also be used to assess progress upon commencement of treatment.
Treatment and prognosis
Although no definitive cure exists, treatment with enzyme replacement therapy has been shown to prolong life. Patients are encouraged to eat a high protein diet to compensate for the loss of muscle strength. Respiratory toilet is recommended in infants.
Patients with the infantile-onset type usually do not reach their first birthday. The later onset types are usually much milder and carry a favorable prognosis.
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- 2. Morales J & Anilkumar A. Glycogen Storage Disease Type II. 2022. - Pubmed
- 3. Prater S, Patel T, Buckley A et al. Skeletal Muscle Pathology of Infantile Pompe Disease During Long-Term Enzyme Replacement Therapy. Orphanet J Rare Dis. 2013;8(1):90. doi:10.1186/1750-1172-8-90 - Pubmed
- 4. Hwang H, Hsu T, Lee Y, Wang H, Chiou H, Niu D. Muscle Ultrasound: A Useful Tool in Newborn Screening for Infantile Onset Pompe Disease. Medicine (Baltimore). 2017;96(44):e8415. doi:10.1097/MD.0000000000008415 - Pubmed
- 5. Quan J, Liu L, Lyu T, Huang X, Tian J. Atypical Infantile-Onset Pompe Disease with Hypertrophic Cardiomyopathy. Chin Med J (Engl). 2017;130(19):2393-4. doi:10.4103/0366-6999.215340 - Pubmed
- 5. Figueroa-Bonaparte S, Segovia S, Llauger J et al. Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function. PLoS One. 2016;11(10):e0163493. doi:10.1371/journal.pone.0163493 - Pubmed
- 7. Cinnamon J, Slonim A, Black K, Gorey M, Scuderi D, Hyman R. Evaluation of the Lumbar Spine in Patients with Glycogen Storage Disease: CT Demonstration of Patterns of Paraspinal Muscle Atrophy. AJNR Am J Neuroradiol. 1991;12(6):1099-103. PMC8331489 - Pubmed