Clinical characteristics: Pompe disease is classified by age of onset, organ involvement, severity, and rate of progression.
Diagnosis/testing: The diagnosis of GSD II is established in a proband with either deficiency of acid alpha-glucosidase enzyme activity or biallelic pathogenic variants in GAA on molecular genetic testing.
Management: Treatment of manifestations: Management guidelines from the American College of Medical Genetics: individualized care of cardiomyopathy as standard drugs may be contraindicated and risk for tachyarrhythmia and sudden death is high; physical therapy for muscle weakness to maintain range of motion and assist in ambulation; surgery for contractures as needed; nutrition/feeding support. Respiratory support may include inspiratory/expiratory training in affected adults, CPAP, BiPAP, and/or tracheostomy. Prevention of primary manifestations: Begin enzyme replacement therapy (ERT) with alglucosidase alfa as soon as the diagnosis is established. Of note, ERT can be accompanied by infusion reactions (which are treatable) as well as anaphylaxis. Infants at high risk for development of antibodies to the therapeutic enzyme are likely to need immunomodulation early in the treatment course. Prevention of secondary complications: Aggressive management of infections; keeping immunizations up to date; annual influenza vaccination of the affected individual and household members; respiratory syncytial virus (RSV) prophylaxis (palivizumab) in the first two years of life; use of anesthesia only when absolutely necessary. Surveillance: Routine monitoring of respiratory status, cardiovascular status, musculoskeletal function (including bone densitometry), nutrition and feeding, renal function, and hearing. Agents/circumstances to avoid: Digoxin, ionotropes, diuretics, and afterload-reducing agents, as they may worsen left ventricular outflow obstruction in some stages of the disease; hypotension and volume depletion; exposure to infectious agents. Evaluation of relatives at risk: Evaluate at-risk sibs to permit early diagnosis and treatment with ERT.
Genetic counseling: Pompe disease is inherited in an autosomal recessive manner. At conception, each sib 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. If the GAA pathogenic variants in an affected family member are known, carrier testing for at-risk family members, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.
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