• Test code: 06157
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Liver Glycogen Storage Disease Panel

Test description

The Invitae Liver Glycogen Storage Disease panel analyzes 11 genes associated with liver glycogen storage diseases (GSDs). This panel may be appropriate for individuals with signs and symptoms of a hepatic GSD including recurrent hypoglycemia and hepatomegaly. Additionally, this panel may be appropriate for those in whom a GSD is suspected due abnormal laboratory values or abnormal liver biopsy. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions.

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Primary panel (11 genes)


Gene Disorders
AGL GSD III (Cori / Forbe disease or Debrancher)
FBP1 Fructose-1,6-bisphosphatase deficiency
G6PC GSD1a (Von Gierke disease)
GBE1 GSD IV (Andersen disease, Brancher enzyme)
GYS2 GSD 0 (Glycogen synthase, liver isoform)
PYGL GSD VI (Hers disease)
SLC2A2 Fanconi-Bickel syndrome
SLC37A4 GSD Ib, c, d

Glycogen storage diseases (GSDs) comprise a constellation of disorders involving the disruption of glycogen metabolism. Glycogen is the storage form of glucose and is present in multiple tissues, but primarily resides in liver and skeletal muscle. It provides a reservoir of glucose for the liver to quickly release during short term fasting, and for muscles to use as fuel source during sudden energy demands or early exercise. Any disruption to the synthesis, release or quality of glycogen can cause a GSD. Each GSD is caused by defects in one specific enzyme and affected individuals have biallelic variants in one gene.

Hepatic GSDs are characterized by recurrent hypoglycemia due to the inability to synthesize glycogen, or release glucose from glycogen stores during times of fasting. In more severe presentations, hypoglycemia can occur as soon as 4 hours after feeding. Acquired hepatomegaly also often occurs secondary to glycogen accumulation in the liver. Additionally, the kidneys and central nervous system can also be affected and secondary metabolic dysfunction leading to gout, hyperlipidemia, neutropenia and lactic acidosis frequently occur. Age of onset, severity of symptoms and risk of mortality is variable amongst the GSDs and is specific to each disease and degree of metabolic control.

Treatment for hepatic GSDs primarily revolves around the use of frequent high carbohydrate food sources to prophylactically prevent hypoglycemia. Additionally, medications to address secondary complications such as gout and hyperlipidemia are also frequently employed. Liver transplant has also successfully been used to treat some of the GSDs.

The GSDs are inherited in an autosomal recessive pattern, with the exception of GSD IXa; which is inherited in an X-linked fashion.

The glycogen storage diseases are individually rare, with incidences averaging around 1:100,000. Certain ethnicities may have a higher prevalence of specific glycogen storage diseases. GDS I, III and IX represent approximately 80% of the GSDs.

  • GSD III 1:100,00 general pop, 1:2500 in Inuits of Nunavik
  • GSD VI 1:100,000
  • 1:1000 in the Mennonite population due to the founder variant c.1620+1G>A. I

This test is appropriate for any individual with any combination of clinical features consistent with a hepatic GSD including recurrent hypoglycemia with or without hepatomegaly.

  1. Ozen, H. Glycogen storage diseases: new perspectives. World J. Gastroenterol. 2007; 13(18):2541-53. PMID: 17552001
  2. Heller, S, et al. Nutritional therapy for glycogen storage diseases. J. Pediatr. Gastroenterol. Nutr. 2008; 47 Suppl 1:S15-21. PMID: 18667910
  3. Dagli, A, et al. Glycogen Storage Disease Type III. 2010 Mar 09. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301788
  4. Dagli, AI, Weinstein, DA. Glycogen Storage Disease Type VI. 2009 Apr 23. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301760
  5. Kishnani, PS, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet. Med. 2014; 16(11):e1. PMID: 25356975
  6. Rake, JP, et al. Guidelines for management of glycogen storage disease type I - European Study on Glycogen Storage Disease Type I (ESGSD I). Eur. J. Pediatr. 2002; 161 Suppl 1:S112-9. PMID: 12373584
  7. Visser, G, et al. Consensus guidelines for management of glycogen storage disease type 1b - European Study on Glycogen Storage Disease Type 1. Eur. J. Pediatr. 2002; 161 Suppl 1:S120-3. PMID: 12373585
  8. Kishnani, PS, et al. Glycogen storage disease type III diagnosis and management guidelines. Genet. Med. 2010; 12(7):446-63. PMID: 20631546
  9. Bhattacharya, K. Investigation and management of the hepatic glycogen storage diseases. Transl Pediatr. 2015; 4(3):240-8. PMID: 26835382
  10. Kilimann, MW, Oldfors, A. Glycogen pathways in disease: new developments in a classical field of medical genetics. J. Inherit. Metab. Dis. 2015; 38(3):483-7. PMID: 25376534
  11. Roach, PJ, et al. Glycogen and its metabolism: some new developments and old themes. Biochem. J. 2012; 441(3):763-87. PMID: 22248338

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AGL NM_000642.2
FBP1 NM_000507.3
G6PC NM_000151.3
GBE1 NM_000158.3
GYS2 NM_021957.3
PHKA2 NM_000292.2
PHKB NM_000293.2; NM_001031835.2
PHKG2 NM_000294.2
PYGL NM_002863.4
SLC2A2 NM_000340.1
SLC37A4 NM_001164277.1