ArtsAutosBooksBusinessEducationEntertainmentFamilyFashionFoodGamesGenderHealthHolidaysHomeHubPagesPersonal FinancePetsPoliticsReligionSportsTechnologyTravel

Genetic Disorders - Pompe

Updated on May 7, 2016


Pompe disease is a type II glycogen storage disease where glycogen accumulates in the lysosomes of certain organs and tissues, especially muscles, impeding their function. This is due to deficiency of the lysosomal acid alpha-1,4 glucosidase enzyme, which hydrolyses the alpha 1–4 and alpha 1–6 bonds in lysosomal glucose polymers. Pompe disease is classified into three groups depending on severity (alpha-glucosidase levels) and age of onset. These types are known as classic infantile-onset, non-classic infantile-onset, and late-onset.

Process for Diagnosis

Diagnosis is made by estimating the acid alpha glucosidase activity in either skin biopsy (fibroblasts), muscle biopsy or in white blood cells. In general, less than 3% of normal enzyme activity is found in severe infantile cases and residual levels ranging 3-30% of normal levels are found in less severe late onset form.

Genes Affected and Chromosomal Locus

The disease is caused by a mutation in the acid alpha glucosidase gene, which codes for the enzyme acid alpha-1,4 glucosidase, on long arm of chromosome 17 at 17q25.2-q25.3. The gene spans approximately 20 kb and contains 20 exons with the first exon being noncoding. There are over 300 mutations associated with the disorder, however, the transversion (T → G) mutation, which interrupts the RNA splicing, is the most common mutation among adults with this disorder. Additionally, a large deletion of exon 18 has been identified in 58% of GAA alleles in patients with both infantile and adult-onset Pompe from diverse ethnic backgrounds.

The chromosomal locus of the acid aloha glucosidase gene.
The chromosomal locus of the acid aloha glucosidase gene.

Metabolic Pathways Disrupted

Acid alpha 1,4 glucosidase cleaves glycogen 1,4 and 1,6 alpha-glycosidic linkages. Its action gives rise to free glucose molecules. Thus, a lack of the enzyme results in a build-up of glycogen in the lysosomes, lysosomal swelling, cellular damage and dysfunction.

Inheritance Pattern and Frequency

The condition is autosomal recessive, with both parents having one copy of the mutated gene but not displaying the symptoms themselves. It has been suggested that the frequency of Pompe’s disease is around 1 in 40,000 people.

Effect of Mutation on RNA Product

Frameshift mutations of GAA, which have been found to be associated with most early-onset phenotypes, lead to a truncated alpha-glucosidase protein with a loss of function.

Effect of Mutation on Cellular Function and Phenotype

The cellular pathology mainly affects muscle fibers (they displace their myofibrils which ultimately leads to skeletal muscle weakness), but also other tissues such as cardiac and smooth muscle cells. The classical form occurs soon after birth and is characterized by hypertrophic cardiomyopathy, cardiorespiratory failure and generalized marked muscle weakness with floppy infant syndrome; if not diagnosed and early treated, the infants rarely survive beyond the first year of life.

The later onset forms have generally a milder phenotype than the classical form and can present with symptoms any time after age 1 year. Cardiac involvement is very rare and symptoms are dominated by significant involvement of skeletal muscles with a gradually progressing myopathy and respiratory insufficiency.


Enzyme replacement therapy with recombinant human acid α-glucosidase can be used to treat all types of Pompes disease, and studies have shown that the therapy significantly prolongs survival, decreases cardiomegaly, and improves cardiac and skeletal muscle function.


    0 of 8192 characters used
    Post Comment

    No comments yet.


    This website uses cookies

    As a user in the EEA, your approval is needed on a few things. To provide a better website experience, uses cookies (and other similar technologies) and may collect, process, and share personal data. Please choose which areas of our service you consent to our doing so.

    For more information on managing or withdrawing consents and how we handle data, visit our Privacy Policy at:

    Show Details
    HubPages Device IDThis is used to identify particular browsers or devices when the access the service, and is used for security reasons.
    LoginThis is necessary to sign in to the HubPages Service.
    Google RecaptchaThis is used to prevent bots and spam. (Privacy Policy)
    AkismetThis is used to detect comment spam. (Privacy Policy)
    HubPages Google AnalyticsThis is used to provide data on traffic to our website, all personally identifyable data is anonymized. (Privacy Policy)
    HubPages Traffic PixelThis is used to collect data on traffic to articles and other pages on our site. Unless you are signed in to a HubPages account, all personally identifiable information is anonymized.
    Amazon Web ServicesThis is a cloud services platform that we used to host our service. (Privacy Policy)
    CloudflareThis is a cloud CDN service that we use to efficiently deliver files required for our service to operate such as javascript, cascading style sheets, images, and videos. (Privacy Policy)
    Google Hosted LibrariesJavascript software libraries such as jQuery are loaded at endpoints on the or domains, for performance and efficiency reasons. (Privacy Policy)
    Google Custom SearchThis is feature allows you to search the site. (Privacy Policy)
    Google MapsSome articles have Google Maps embedded in them. (Privacy Policy)
    Google ChartsThis is used to display charts and graphs on articles and the author center. (Privacy Policy)
    Google AdSense Host APIThis service allows you to sign up for or associate a Google AdSense account with HubPages, so that you can earn money from ads on your articles. No data is shared unless you engage with this feature. (Privacy Policy)
    Google YouTubeSome articles have YouTube videos embedded in them. (Privacy Policy)
    VimeoSome articles have Vimeo videos embedded in them. (Privacy Policy)
    PaypalThis is used for a registered author who enrolls in the HubPages Earnings program and requests to be paid via PayPal. No data is shared with Paypal unless you engage with this feature. (Privacy Policy)
    Facebook LoginYou can use this to streamline signing up for, or signing in to your Hubpages account. No data is shared with Facebook unless you engage with this feature. (Privacy Policy)
    MavenThis supports the Maven widget and search functionality. (Privacy Policy)
    Google AdSenseThis is an ad network. (Privacy Policy)
    Google DoubleClickGoogle provides ad serving technology and runs an ad network. (Privacy Policy)
    Index ExchangeThis is an ad network. (Privacy Policy)
    SovrnThis is an ad network. (Privacy Policy)
    Facebook AdsThis is an ad network. (Privacy Policy)
    Amazon Unified Ad MarketplaceThis is an ad network. (Privacy Policy)
    AppNexusThis is an ad network. (Privacy Policy)
    OpenxThis is an ad network. (Privacy Policy)
    Rubicon ProjectThis is an ad network. (Privacy Policy)
    TripleLiftThis is an ad network. (Privacy Policy)
    Say MediaWe partner with Say Media to deliver ad campaigns on our sites. (Privacy Policy)
    Remarketing PixelsWe may use remarketing pixels from advertising networks such as Google AdWords, Bing Ads, and Facebook in order to advertise the HubPages Service to people that have visited our sites.
    Conversion Tracking PixelsWe may use conversion tracking pixels from advertising networks such as Google AdWords, Bing Ads, and Facebook in order to identify when an advertisement has successfully resulted in the desired action, such as signing up for the HubPages Service or publishing an article on the HubPages Service.
    Author Google AnalyticsThis is used to provide traffic data and reports to the authors of articles on the HubPages Service. (Privacy Policy)
    ComscoreComScore is a media measurement and analytics company providing marketing data and analytics to enterprises, media and advertising agencies, and publishers. Non-consent will result in ComScore only processing obfuscated personal data. (Privacy Policy)
    Amazon Tracking PixelSome articles display amazon products as part of the Amazon Affiliate program, this pixel provides traffic statistics for those products (Privacy Policy)