Pompe disease, also known as Glycogen storage disease type II and Acid maltase deficiency
Pompe disease is a lysosomal storage disease and is caused by a deficiency of acid alpha-glucosidase (GAA). Pompe disease is inherited as an autosomal recessive disorder. There are two types of Pompe disease: infantile-onset and late-onset. In the infantile-onset form of Pompe disease, the earliest symptoms occur in the first weeks of life. In the late-onset form, the first symptoms occur in childhood or early adulthood. It is estimated that incidence of Pompe disease is about 1 in 40,000 births in the United States.
Newborns with infantile-onset Pompe disease often do not show signs of the condition. Within the first months of life, parents may notice feeding problems, irritability, poor head control, and a protruding tongue. The child may also have hypotonia and absent reflexes, respiratory distress and/or hepatomegaly. A chest X-ray, echocardiogram, or electrocardiogram may show an enlarged heart consistent with hypertrophic cardiomyopathy. The disease is progressive and usually fatal in the first year of life.
A person with late-onset Pompe disease does not show symptoms of the condition at birth. As children, individuals with late-onset Pompe disease may seem clumsy, have decreased stamina, or have difficulty performing certain activities, such as sit-ups. The disease is often not diagnosed, however, until individuals have more severe symptoms including lower extremity and truncal muscle weakness, resulting in decreased ambulation, shortness of breath, scoliosis, and back pain.
Pompe disease can be confirmed by documenting absent or deficient acid alpha-glucosidase (GAA) in skin fibroblasts or by documenting the presence of biallelic pathogenic variants in the GAA gene.
• Poor feeding / failure to thrive
• Motor delay/muscle weakness
• Respiratory infections/difficulty
• Cardiac abnormalities
• Abnormal newborn screening results suggestive of Pompe disease
PCR-based sequencing of entire coding region, intron/exon boundaries, as well as known pathogenic variants (HGMD 2017.3) in the promoter and deep intronic regions of the specified gene(s).
Sensitivity and Limitations
The analytical sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed. Variants in regulatory regions and non-reported variants in untranslated regions may not be detected by this test. Large deletions/ duplications, large insertions and other complex genetic events will not be identified using sequencing methodology.
• GAA full gene sequence analysis: 81406
• GAA family specific variant analysis: 81403
How to Order
Testing for this gene is also available as part of the Metaboseq panel by next-generation sequencing and the Glycogen Storage Disease panel by next-generation sequencing. Deletion/duplication analysis and targeted variant analysis is also available for this gene. Download Inborn Errors of Metabolism requisition.
Chan J., et al. (2017) The emerging phenotype of late-onset Pompe disease: A systematic literature review. Mol Genet Metab. 2017 Mar;120(3):163-172.
De Filippi P., et al. (2014) Genotype-phenotype correlation in Pompe disease, a step forward. Orphanet J Rare Dis. 2014 Aug 8;9:102.
Kishnani PS., et al. (2006) Pompe disease diagnosis and management guideline. Genet Med. 2006 May;8(5):267-88.
Kroos M. et al (2008) Update of the Pompe disease mutation database with 107 sequence variants and aformat for severity rating. Hum Mutat. 2008 Jun;29(6):E13-26. doi: 10.1002/humu.20745.
Martiniuk F. et al (1991) Isolation and partial characterization of the structural gene for human acidalpha glucosidase. DNA Cell Biol. 1991 May;10(4):283-92.
Richard E. et al (2011) New insights into therapeutic options for Pompe disease. IUBMB Life. 2011 Nov;63(11):979-86. doi: 10.1002/iub.529. Epub 2011 Oct 14.
Schoser B., et al. (2017) Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis. J Neurol. 2017 Apr;264(4):621-630.
Wang RY. et al (2011) Lysosomal storage diseases: diagnostic confirmation and management ofpresymptomatic individuals. Genet Med. 2011 May;13(5):457-84. doi: 10.1097/GIM.0b013e318211a7e1.