AGL, ALDOA, ENO3, G6PC, GAA, GBE1, GYS1, GYS2, PFKM, PGAM2, PHKA1, PHKA2, PHKB, PHKG2, PRKAG2, PYGL, PYGM, SLC2A2, and SLC37A4
Glycogen storage diseases and related disorders
Glycogen storage diseases (GSDs) result due to errors in glycogen metabolism leading to its improper storage in different tissues. The incidence of GSDs is about 1 in 20-25,000 and the most common types are I, II, III and IV. About 90% of patients with GSDs have types I through IV, however, types 0, VI and IX have mild symptoms and may be underdiagnosed. Symptoms vary based on the type of GSD, some GSDs primarily affect liver, whereas others affect muscles.
• Hepatomegaly, liver dysfunction and cirrhosis
• Hypotonia and muscle cramps
• Respiratory distress
• Growth retardation
This test is performed by enrichment of the coding exons, flanking intronic and untranslated regions (5’ and 3’), as well as known pathogenic variants (HGMD 2017.3) in the promoter and deep intronic regions of the genes specified above using oligonucleotide probe hybridization followed by next-generation sequencing with >50X coverage at every target base. All pathogenic and novel variants, as well as variants of unknown (indeterminate) significance, as determined bioinformatically, are confirmed by Sanger sequencing. Regions with <50X will be filled in by Sanger sequencing. A detailed non-coding variant list is available upon request.
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.
How to Order
These genes are also included as part of the Metaboseq panel. A “Reflex to Metaboseq Panel” can be ordered with the Glycogen Storage Disease panel. If primary test results are negative or do not fully explain the patient’s clinical symptoms, the Metaboseq panel will automatically be performed when “Reflex to Metaboseq panel” is also ordered. Download Inborn Errors of Metabolism requisition.
Bhattacharya, K. (2015) Investigation and management of the hepatic glycogen storage diseases. Transl Pediatr. 4(3):240-8.
Burda, P and Hochuli, M. (2015) Hepatic glycogen storage disorders: what have we learned in recent years? Curr Opin Clin Nutr Metab Care. 18(4):415-21.
Chandramouli, C, Varma, U, et al. (2015) Myocardial glycogen dynamics: new perspectives on disease mechanisms. Clin Exp Pharmacol Physiol. 42(4):415-25.
Kanungo, S, Wells K, et al. (2018) Glycogen metabolism and glycogen storage disorders. Ann Transl Med. 6(24):474.
Kilimann, MW and Oldfors, A. (2015) Glycogen pathways in disease: new developments in a classical field of medical genetics. J Inherit Metab Dis. 38(3):483-7.
Stone, WL and Adil, A. Glycogen Storage Disease. StatPearls [Internet].
Sun, B, Brooks, ED, et al. (2015) Preclinical Development of New Therapy for Glycogen Storage Diseases. Curr Gene Ther. 15(4):338-47.
Weinstein, DA, Steuerwald, U et al. (2018) Inborn Errors of Metabolism with Hypoglycemia: Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis. Pediatr Clin North Am. 65(2):247-265.