GAA gene

Also known as: Glycogen Storage Disease II; GSD II; Acid Alpha-Glucosidase Deficiency; GAA Deficiency; Glycogenosis, Generalized, Cardiac Form; Cardiomegalia Glycogenica Diffusa; Acid Maltase Deficiency; AMD; Alpha-1,4-Glucosidase Deficiency


1. The Disease

A rare lysosomal storage disease characterized by lysosomal accumulation of glycogen particularly in skeletal, cardiac, and respiratory muscles, as well as the liver and nervous system, due to acid maltase deficiency. The clinical spectrum comprises infantile-onset disease with severe hypertrophic cardiomyopathy, generalized muscle weakness, poor feeding and failure to thrive, and respiratory insufficiency; and late-onset disease manifesting before or after twelve months of age without cardiomyopathy, with proximal muscle weakness and respiratory insufficiency.

2. The Symptoms

Pompe disease (PD) is classified by age of onset, organ involvement, severity, and rate of progression. Lack of early signs or symptoms does not exclude the diagnosis.

  • 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.
  • 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.

3. Actions to take in case of early diagnosis

  • Babies should have confirmatory test for Pompe disease through the measurement of acid alpha-glucosidase enzyme activity in white blood cells or filter paper.
  • As the clinical manifestations of PD are multisystemic, a multidisciplinary approach is required to proactively recognize and manage complications. Routine assessment of the various affected organs is necessary, and each specialist in the multidisciplinary team should oversee continuing evaluations once a clinical problem is identified.
  • 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.
  • 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.
  • LOPD: ERT may stabilize the functions most likely to be lost: respiration and motor ability.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information