Glycogen storage disease type II, also known as Pompe disease or acid maltase deficiency disease, is an inherited lysosomal 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.
Echocardiogram may also reveal a hypertrophic left ventricle and hypertrophic septum 5.
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 glutei 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 favourable prognosis.
Sparing of the psoas muscles suggests glycogen storage disease type V (McArdle disease) 7.
- 1. Howell RR, Byrne B, Darras BT, Kishnani P, Nicolino M, van der Ploeg A. Diagnostic challenges for Pompe disease: an under-recognized cause of floppy baby syndrome. (2006) Genetics in medicine : official journal of the American College of Medical Genetics. 8 (5): 289-96. doi:10.109701.gim.0000204462.42910.b8 - Pubmed
- 2. Jose A. Morales, Steve S. Bhimji. Glycogen Storage Disease, Type II (Pompe Disease). (2017) Pubmed
- 3. Sean N Prater, Trusha T Patel, Anne F Buckley, Hanna Mandel, Eugene Vlodavski, Suhrad G Banugaria, Erin J Feeney, Nina Raben, Priya S Kishnani. Skeletal muscle pathology of infantile Pompe disease during long-term enzyme replacement therapy. (2013) Orphanet Journal of Rare Diseases. 8 (1): 90. doi:10.1186/1750-1172-8-90 - Pubmed
- 4. Hwang HE, Hsu TR, Lee YH, Wang HK, Chiou HJ, Niu DM. Muscle ultrasound: A useful tool in newborn screening for infantile onset pompe disease. (2017) Medicine. 96 (44): e8415. doi:10.1097/MD.0000000000008415 - Pubmed
- 5. Quan JJ, Liu LJ, Lyu TW, Huang XP, Tian J. Atypical Infantile-onset Pompe Disease with Hypertrophic Cardiomyopathy. (2017) Chinese medical journal. 130 (19): 2393-2394. doi:10.4103/0366-6999.215340 - Pubmed
- 5. Figueroa-Bonaparte S, Segovia S, Llauger J, Belmonte I, Pedrosa I, Alejaldre A, Mayos M, Suárez-Cuartín G, Gallardo E, Illa I, Díaz-Manera J. Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function. (2016) PloS one. 11 (10): e0163493. doi:10.1371/journal.pone.0163493 - Pubmed
- 7. Cinnamon J, Slonim AE, Black KS, Gorey MT, Scuderi DM, Hyman RA. Evaluation of the lumbar spine in patients with glycogen storage disease: CT demonstration of patterns of paraspinal muscle atrophy. (1991) AJNR. American journal of neuroradiology. 12 (6): 1099-103. Pubmed