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), cardiomyopathy and muscular hypotonia are the cardinal
features. In the juvenile and adult forms, involvement of skeletal muscles
dominates the clinical presentation.
Acid Maltase Deficiency; Pompe Syndrome; Pompe Disease;
Cardiomegalia Glycogenica Diffusa; Cardiac form of Generalized Glycogenosis;
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
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.
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
There are three major forms of the disorder.
- Infantile Form: 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 with
open mouth and protruding tongue. 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. Normal blood glucose concentration.
No effective treatment. Death usually results from respiratory failure,
which is often complicated by aspiration pneumonia and/or congestive cardiac
failure. The disease is rapidly progressive, and few children survive beyond the
age of 1 year. Death usually results from respiratory failure and/or end-stage cardiomyopathy.
Two different recombinant human α-glucosidase enzymes are now available, which showed an improved outcome