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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.

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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.

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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.

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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.

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

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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.

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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.

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There are three major forms of the disorder.

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  • 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 for ...

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