Pompe Disease

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: Pompe disease is classified by age of onset, organ involvement, severity, and rate of progression.

  1. Infantile-onset Pompe disease (IOPD; individuals with onset before age 12 months with cardiomyopathy) may be apparent in utero but more typically onset is at the median age of four months with hypotonia, generalized muscle weakness, feeding difficulties, failure to thrive, respiratory distress, and hypertrophic cardiomyopathy. Without treatment by enzyme replacement therapy (ERT), IOPD commonly results in death by age two years from progressive left ventricular outflow obstruction and respiratory insufficiency.

  2. Late-onset Pompe disease (LOPD; including: (a) individuals with onset before age 12 months without cardiomyopathy; and (b) all individuals with onset after age 12 months) is characterized by proximal muscle weakness and respiratory insufficiency; clinically significant cardiac involvement is uncommon.

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.

  1. IOPD. In the pivotal trial, a majority of infants in whom ERT was initiated before age six months and before the need for ventilatory assistance showed improved survival, ventilator-independent survival, improved acquisition of motor skills, and reduced cardiac mass compared to untreated controls. More recent data suggest that initiation of ERT before age two weeks may improve motor outcomes in the first two years of life, even when compared to infants in whom treatment was initiated only ten days later.

  2. LOPD. ERT may stabilize the functions most likely to be lost: respiration and motor ability.

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, kidney 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.

Publication types

  • Review