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At a glance

Inborn error of metabolism that results from the deficiency of acid alpha-glucosidase, a lysosomal hydrolase. The three variants are infantile, juvenile, and adult onset. In the classic infantile form (Pompe disease), severe hypertrophic cardiomyopathy, and muscular hypotonia are the cardinal features. In the juvenile and adult forms, involvement of skeletal muscles (progressive muscular hypotonia) and respiratory failure dominates the clinical presentation.


Acid Maltase Deficiency; Pompe Syndrome; Pompe Disease; Cardiomegalia Glycogenica Diffusa; Cardiac Generalized Glycogenosis Syndrome; GAA Deficiency; Alpha-1,4-Glucosidase Deficiency; Glycogenosis Type II.


First described by the Dutch pathologist Joannes Cassianus Pompe (1901-1945) in 1932, when he reported a 7-month-old girl who died after developing idiopathic hypertrophic cardiomyopathy.


In the United States, the frequency is estimated at 1:40,000 live births for all three variants of GSD II. Internationally, the frequency in Taiwan and southern China is estimated at 1:50,000 individuals. In the Dutch population, the frequency is 1:40,000 (1:138,000 for the infantile category). In this population, 63% carry at least one of the three common mutations.

Genetic inheritance

Autosomal recessive. The gene for the affected enzyme has been mapped to 17q25.2-q25.3.


Absent acid alpha-1,4-glucosidase (acid maltase), a lysosomal enzyme, in muscle and liver. The enzyme degrades alpha-1,4 and alpha-1,6 linkages in glycogen, maltose, and isomaltose. Deficiency of the enzyme results in accumulation of glycogen within lysosomes and in the cytoplasm, eventually leading to tissue destruction.


Neonates appear normal at birth but develop hypotonia and poor feeding within a few weeks. Specific enzyme assay in muscle cells, leukocytes, or amniocytes confirms the diagnosis. Creatine kinase elevation, muscle biopsy, demonstration of massive glycogen deposits in lymphocytes in peripheral blood, measurement of acid alpha-1,4-glucosidase activity in leukocytes.

Clinical aspects

There are three major forms of the disorder.

  • Infantile Form (Pompe Disease): Infants may appear normal at birth but after a few weeks they begin to develop cardiomyopathy and generalized hypotonia and muscle weakness, which are the cardinal features of the disease. Biventricular hypertrophy and either congestive or obstructive cardiomyopathy result from the accumulation of glycogen, which leads to progressive cardiac failure. Poor swallowing reflexes and decreased muscle tone contribute to feeding difficulties and aspiration. An enlarged tongue (macroglossia) and diminished airway reflexes may cause upper airway obstruction. Characteristic facial appearance includes an open mouth and protruding tongue at all times. The ECG classically shows signs of biventricular hypertrophy with a short PR interval. The chest radiograph confirms the presence of cardiomegaly and may show evidence of atelectasis and aspiration. The liver is not affected, although it may be enlarged as a result of cardiac failure. Normal mental development is ...

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