Pompe Disease

Original Editor - Chelsea Mclene Top Contributors - Nupur Smit Shah, Chelsea Mclene, Kim Jackson and Lucinda hampton  

Introduction[edit | edit source]

Glycogen-metabolism, disrupted in Pompe disease

Pompe disease is an inherited genetic disorder known as metabolic myopathy; it is also referred to as glycogen storage disease(type 2). Here there is a deficiency of acid glucosidase(GAA). This leads to the lysosomal accumulation of glycogen in all the cells which causes abnormal myofibrillogenesis in the striated muscles.[1] In normal conditions, GAA is responsible for the acceleration of intralysosomal degradation of glycogen.

It is a rare, progressive, inherited, and often fatal muscular disease[2] - it affects one in 40000 children.[3] It disables the heart and skeletal muscles and is caused by mutations in a gene that makes an enzyme called acid alpha-glucosidase (GAA)[4]. It is also an autosomal recessive disorder due to deficiency of a lysosomal enzyme, acid maltase. It affects both males and females.


Causes and Inheritance[edit | edit source]

Glycogen structure.jpeg

Glycogen is a form of sugar that the body stores in cells of the liver and skeletal muscles, and works as a long-term reserve of energy. When the body needs energy, this large molecule is broken down into smaller molecules of a simpler sugar called glucose. Certain proteins are needed for this process. A mutation in the GAA gene can either prevent the production of this enzyme, or create an enzyme that does not work as intended. In either case, glycogen cannot be broken down and builds to toxic levels inside cells, impairing certain organs and systems, particularly the muscles.

Pompe disease is inherited in autosomal recessive disorder which means the disease only develops in people who inherit two faulty copies of the gene, one from each parent. The signs and symptoms are not seen in individuals who have one faulty gene. They are called carriers because they can pass the disease onto their children. When both parents are carriers, child has 50 percent chance of inheriting one mutated gene and also becoming a carrier, and a 25 percent chance of inheriting two healthy genes and neither developing the disease nor being a carrier.[6][7][8]

Types[edit | edit source]

Infantile Onset Pompe disease: Characterized by Cardiomyopathy, respiratory insufficiency, and severe hypotonia.

Late-Onset Pompe disease: Usually begins at any time between one year of age to adulthood. Characterized by fatigue, exercise intolerance, and myalgia. It progresses to severe motor disability and respiratory insufficiency. Infantile form, childhood, Juvenile, and adult glycogen storage disease is classified as LOPD (late-onset Pompe disease)

Classic infantile-onset[edit | edit source]

It appears within a few months of birth. Infants experience muscle weakness, poor muscle tone, an enlarged liver, breathing problem, heart defects, fails to gain weight and grow at the expected rate. If untreated, leads to death from heart failure in the first year of life.

Non-classic infantile-onset[edit | edit source]

It appears at about 1 year of age. It is characterized by delayed motor skills and progressive muscle weakness. The heart may be abnormally large, but affected individuals usually do not experience heart failure. The muscle weakness in this disorder leads to serious breathing problems, and most children live only into early childhood.

Symptoms[edit | edit source]

Classic Infantile[edit | edit source]

  • Weak muscles
  • Poor muscle tone
  • Feeding problems
  • Infections in the respiratory system
  • Problems with hearing
  • Enlarged liver
  • Failure to gain weight and grow at the expected rate
  • Trouble breathing

Non-classic Infantile[edit | edit source]

  • Motor skills delayed
  • Breathing problems
  • Muscles get steadily weaker
  • Abnormally large heart

Late-onset type clinical multisystem involvement[edit | edit source]

Organ invlovement Clinical Manifestation
Skeletal muscles Axial muscles as more affected than lower limb

Exercise intolerance

Scapula winging


Respiratory Sleep apnea


Shortness of breath (dyspnea)

CNS Stroke

Intracranial aneurysm

Sensorineural deafness

Cerebral hemorrhage

Cognitive and Emotional Mild cognitive impairment



CVS Rhythm disturbances

Cardia hypertrophy

Musculoskeletal Vertebral fractures

Bent spine syndrome





Peripheral and Autonomic nervous system Burning and Paraesthesia

Diagnosis[edit | edit source]

Enzyme activity tests[edit | edit source]

Skin biopsy and blood tests are done to find out the deficiency of the acid alpha-glucosidase enzyme.

Genetic testing[edit | edit source]

The aim is to identify disease-causing mutations in the GAA gene.

MRI , Chest X-ray, ECG and Echo-cardiogram and laboratory tests[edit | edit source]

Chest X-ray is done to rule out cardiomyopathy.

ECG is done to check the conduction of impulses and Echo is done to check the functioning of the heart muscle.

Creatine kinase (CK) in the blood (usually elevated in heart damage) and liver enzyme changes are ruled out via laboratory tests..[10]

Treatment[edit | edit source]

Medical Management[edit | edit source]

Enzyme replacement therapy.

Pompe disease patients are followed by a multidisciplinary team of specialists, including cardiologists, neurologists, pulmonologists, respiratory therapists, metabolic specialists, dietitians, orthopedists, occupational/speech therapists, geneticists, and genetic counselors. Enzyme replacement therapy may help reduce the buildup of glycogen inside cells, and slow the progression of the disease. A drug called alglucosidase alfa is given intravenously. It is a genetically engineered enzyme that acts like the naturally occurring acid alfa glucosidase enzyme.[11][12]

Physiotherapy Mangement[edit | edit source]

A physiotherapist can help by implementing and monitoring a light exercise routine that may involve walking, cycling, swimming or strength training to maintain muscle strength in people with Pompe disease. It is important to not perform excessively strenuous exercise, though, because it may cause more muscle damage.[13]


References[edit | edit source]

  1. Rucker M, Fraites Jr TJ, Porvasnik SL, Lewis MA, Zolotukhin I, Cloutier DA, Byrne BJ. Rescue of enzyme deficiency in embryonic diaphragm in a mouse model of metabolic myopathy: Pompe disease.
  2. Vissing J, Lukacs Z, Straub V. Diagnosis of Pompe disease: muscle biopsy vs blood-based assays. JAMA neurology. 2013 Jul 1;70(7):923-7.
  3. Jones A, Duran I, Stark C, Spiess K, Semler O, Schoenau E. Vibration assisted rehabilitation in patients with Pompe disease: A case series. Journal of musculoskeletal & neuronal interactions. 2022 Mar 1;22(2):284-91.
  4. NIH. Pompe disease information page. Available from https://www.ninds.nih.gov/Disorders/All-Disorders/Pompe-Disease-Information-Page#:~:text=Definition,alpha%2Dglucosidase%20(GAA). [last accessed 04/01/2021]
  5. Pompe disease - causes, symptoms, diagnosis, treatment, pathology. Osmosis. Available from https://www.youtube.com/watch?v=ecRCw4NKcJ8 [last accessed 05/01/2021]
  6. What is pompe disease? Pompe news. Available from https://pompediseasenews.com/what-is-pompe-disease/ [last accessed 05/01/2021]
  7. Pompe disease. WebMD. Available from https://www.webmd.com/a-to-z-guides/pompe-disease#1 [last accessed 05/01/2020]
  8. Lim JA, Li L, Raben N. Pompe disease: from pathophysiology to therapy and back again. Frontiers in aging neuroscience. 2014 Jul 23;6:177.
  9. Toscano A, Rodolico C, Musumeci O. Multisystem late onset Pompe disease (LOPD): an update on clinical aspects. Annals of translational medicine. 2019 Jul;7(13).
  10. Vissing J, Lukacs Z, Straub V. Diagnosis of Pompe disease: muscle biopsy vs blood-based assays. JAMA neurology. 2013 Jul 1;70(7):923-7.
  11. Chien YH, Hwu WL. A review of treatment of Pompe disease in infants. Biologics: targets & therapy. 2007 Sep;1(3):195.
  12. Chien YH, Hwu WL, Lee NC. Pompe disease: early diagnosis and early treatment make a difference. Pediatrics & Neonatology. 2013 Aug 1;54(4):219-27.
  13. Case LE, Kishnani PS. Physical therapy management of Pompe disease. Genet Med. 2006 May;8(5):318-27. doi: 10.1097/01.gim.0000217789.14470.c5. PMID: 16702883.
  14. Physical Therapy and Pompe Disease. Rare disease report. Available from https://www.youtube.com/watch?v=aR2EVbPYqoI [last accessed 05/01/2021]