Synonyms: glycogen storage disease type II; acid maltase deficiency
Pompe's disease is a glycogen storage disorder. Deficiency of the lysosomal enzyme alpha-1,4-glucosidase (acid maltase) leads to the accumulation of glycogen in many tissues:
- The clinical spectrum is continuous and broad and three major forms are recognised: infantile, juvenile and adult-onset.
- In the infantile form, accumulation of glycogen in cardiac muscle leads to cardiac failure.
- Accumulation may also occur in the liver, which results in hepatomegaly and elevation of hepatic enzymes.
- Glycogen accumulation in muscle and peripheral nerves causes hypotonia and weakness.
- Glycogen deposition in blood vessels may result in intracranial aneurysms.
- The overall prevalence has been estimated at 1 in 40,000, with 1 in 138,000 for the infantile form and 1 in 57,000 for the adult form.
- Pompe's disease has an estimated frequency of 1 in 40,000 in African-American, 1 in 50,000 in Chinese, 1 in 40,000 in Dutch, and 1 in 146,000 in Australian populations.
- Infantile and adult forms are inherited as autosomal recessive conditions. The gene has been traced to chromosome 17.
- Presentation later in life is associated with a less severe form of disease.
- There is a continuous spectrum between the classic infantile and adult forms.
- The infantile form presents in the first six months of life (typically at between 4-8 weeks) with weakness, hypotonia, respiratory distress, feeding difficulties and heart failure.
- The juvenile form presents later in childhood with delayed motor development, muscle weakness and hypotonia.
- The adult form usually presents as skeletal and respiratory muscle weakness. The typical age of presentation is 20-40 years. There may be limb-girdle weakness and weakness of respiratory muscles.
- Infantile form:
- Adult form:
- Weakness may affect only specific muscle groups, eg upper arms, and may be asymmetrical.
- Limb-girdle weakness is common and respiratory muscle involvement may be prominent.
- Other glycogen storage disorders.
- Muscular dystrophy: Duchenne muscular dystrophy (or less severe muscular dystrophies for older-onset disease).
- Serum creatine kinase and aspartate aminotransferase are elevated.
- Definitive diagnosis is made by the measurement of acid alpha-glucosidase activity in cultured skin fibroblasts or peripheral blood lymphocytes.
- Intracranial aneurysms may be shown on angiography or magnetic resonance angiography.
- Echocardiogram to assess heart size and degree of left ventricular hypertrophy.
- ECG: short PR interval and elevated QRS complexes in the infantile form.
- Electromyography (EMG) shows a myopathic pattern and also often shows pseudomyotonic discharges, fibrillation potentials and positive waves.
- Muscle biopsy for the evaluation of differential diagnosis of muscle weakness.
- Enzyme replacement therapy:
- Enzyme replacement therapy has been shown to be very effective and substantially improves the prospects for patients.
- Alglucosidase alfa (Myozyme®), an enzyme produced by recombinant DNA technology, is licensed for long-term replacement therapy in Pompe's disease. Myozyme® is available by referral to an expert centre:
- Paediatric centres in England: Addenbrooke's (Cambridge), Birmingham Children's Hospital, Great Ormond Street Hospital, Willink (Royal Manchester Children's Hospital).
- Adult centres in England: Addenbrooke's, The Hope (Manchester), National Hospital for Neurology and Neurosurgery (London), The Royal Free (London).
- Alglucosidase alfa therapy has been shown to improve cardiac and skeletal muscle function.[10, 11] Therapy has been shown to achieve significant reductions in the risk of death and invasive ventilation among treated patients.
- Treatment of cardiac failure and respiratory failure may be required.
- Diet therapy may provide temporary improvement but does not alter the disease course: a high-protein, low-carbohydrate diet may be beneficial.
- Physiotherapy and occupational therapy may be required.
- Genetic counselling and prenatal diagnosis: chorionic villus sampling and amniocentesis can be used to determine enzyme activity in a fetus.
- Gene therapy remains a potentially effective treatment for the future.
- In the infantile form, cardiomegaly and congestive heart failure lead to death.
- Cardiomegaly with progressive obstruction to left ventricular outflow is a major cause of mortality.
- Aspiration pneumonia; weakness of ventilatory muscles increases the risk of pneumonia.
- The adult form manifests with dystrophy and respiratory muscle weakness.
- In the adult form, intracranial aneurysms present the greatest complication.
- Liver failure may occur.
- Without enzyme replacement therapy, the infantile form is usually fatal, with most deaths occurring within one year of birth.
- Later clinical onset usually corresponds with more benign symptoms and disease course.
- The adult form is not necessarily fatal, but complications, such as rupture of an aneurysm or respiratory failure, may cause significant morbidity and mortality.
Further reading and references
Ibrahim J et al; Genetics of Glycogen-Storage Disease Type II (Pompe Disease), Medscape, Jul 2011
Ausems MG, Verbiest J, Hermans MP, et al; Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet. 1999 Sep7(6):713-6.
van der Ploeg AT, Reuser AJ; Pompe's disease. Lancet. 2008 Oct 11372(9646):1342-53.
Sivak ED, Salanga VD, Wilbourn AJ, et al; Adult-onset acid maltase deficiency presenting as diaphragmatic paralysis. Ann Neurol. 1981 Jun9(6):613-5.
Trend PS, Wiles CM, Spencer GT, et al; Acid maltase deficiency in adults. Diagnosis and management in five cases. Brain. 1985 Dec108 ( Pt 4):845-60.
Ausems MG, Lochman P, van Diggelen OP, et al; A diagnostic protocol for adult-onset glycogen storage disease type II. Neurology. 1999 Mar 1052(4):851-3.
Amalfitano A, Bengur AR, Morse RP, et al; Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genet Med. 2001 Mar-Apr3(2):132-8.
Brady RO, Schiffmann R; Enzyme-replacement therapy for metabolic storage disorders. Lancet Neurol. 2004 Dec3(12):752-6.
Isaacs H, Savage N, Badenhorst M, et al; Acid maltase deficiency: a case study and review of the pathophysiological changes and proposed therapeutic measures. J Neurol Neurosurg Psychiatry. 1986 Sep49(9):1011-8.
Coutelle C, Themis M, Waddington SN, et al; Gene therapy progress and prospects: fetal gene therapy--first proofs of concept--some adverse effects. Gene Ther. 2005 Nov12(22):1601-7.
van den Hout HM, Hop W, van Diggelen OP, et al; The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature. Pediatrics. 2003 Aug112(2):332-40.
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