Genetics of Glycogen-Storage Disease Type II (Pompe Disease) Treatment & Management
- Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD more...
Enzyme replacement therapy (ERT) for the treatment of glycogen-storage disease type II (GSD II) has been available since 2006.[22, 23] A 3-year follow-up revealed significant reductions in the risk of death and invasive ventilation among treated patients. Approximately one-half of patients on ERT develop infusion-associated reactions. However, these are readily managed with premedication using various combinations of antipyretic, anti-inflammatory, and antihistamine medications. The findings of one study suggest that the use of ERT in patients with late-onset Pompe disease did not affect cardiovascular parameters and no cardiovascular safety concerns were noted. Identified cardiovascular abnormalities noted may be related to Pompe disease or other comorbid conditions rather than to ERT.
Symptomatic treatment of cardiac and respiratory failure is available but does not significantly alter the clinical course.
Anecdotal evidence suggests that a high-protein diet can provide temporary improvement; however, such a diet does not alter the disease course.
Preclinical investigation of gene therapy is ongoing.
The use of pharmacological chaperones (oral therapy) is currently under investigation.
A clinical geneticist in concert with a genetic counselor are advised to counsel families regarding risk to future pregnancies.
GSD II (Pompe disease) is inherited in an autosomal-recessive manner. In most cases, the parents of a proband are heterozygotes and thus carry a single copy of a GAA pathogenic variant. Heterozygotes (carriers) are asymptomatic. At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Historically, children with classic infantile-onset GSD II have not survived to reproduce. Individuals with later-onset disease can reproduce, as they can survive into their sixth and seventh decades of life.
Carrier testing using molecular genetic testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic GAA variants in the family are known.
A pediatric cardiologist can provide assessment of all infants, children, and adolescents suspected of having GSD II disease. Experienced interpretation of ECG and echocardiography findings are necessary.
A neurologist can assist with the results and interpretation of EMG findings.
As noted above, alterations in diet do not provide lasting improvement. Weakness can contribute to feeding difficulty in all patients. Infants ultimately may require tube feeding to provide adequate caloric intake. Nutritional support does not change the disease course; hence, some families may choose not to pursue tube feeding for their child when facing such a fatal illness.
Proximal muscle weakness may interfere with the normal daily activities of adult patients. Physical and occupational therapy may prove beneficial.
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