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  • Test code: 06156
  • 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
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Invitae Comprehensive Glycogen Storage Disease Panel

Test description

The Invitae Comprehensive Glycogen Storage Disease panel analyzes 25 genes associated with various glycogen storage diseases (GSDs). This panel may be appropriate for individuals with signs and symptoms of a GSD. Additionally, this panel may be appropriate for those in whom a GSD is suspected due to abnormal laboratory values, muscle or liver biopsy. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions.

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Primary panel (23 genes)

AGL ALDOA ENO3 FBP1 G6PC GAA GBE1 GYG1 GYS1 GYS2 LAMP2 LDHA PFKM PGAM2 PHKA1 PHKA2 PHKB PHKG2 PYGL PYGM RBCK1 SLC2A2 SLC37A4

Add-on fatty acid oxidation genes (21 genes)

ACADM ACADS ACADSB ACADVL CPT1A CPT2 ETFA ETFB ETFDH HADH HADHA HADHB HMGCL HMGCS2 MLYCD NADK2 SLC22A5 SLC25A20 SLC52A1 SLC52A2 SLC52A3

Add-on limited evidence genes (2 genes)

glycogen storage diseases (GSD)

  • primary hepatic GSD
  • primary muscular GSD

Gene Disorder
AGL GSD III (Cori / Forbes disease or Debrancher)
ALDOA GSD XII, Aldolase A deficiency
ENO3 GSD 13
FBP1 Fructose-1,6-bisphosphatase deficiency
G6PC GSD1a (Von Gierke disease)
GAA GSD II (Pompe disease)
GBE1 GSD IV (Andersen disease, Brancher enzyme)
GYG1 GSD XV
GYS1 GSD 0 (Glycogen synthase, muscle isoform)
GYS2 GSD 0 (Glycogen synthase, liver isoform)
LAMP2 GSD IIa (Danon disease)
LDHA GSD XI  (Lactate dehydrogenase deficiency)
PFKM GSD VII
PGAM2 GSD X
PHKA1 GSD IXd (X-linked muscle glycogenosis)
PHKA2 GSD IXa
PHKB GSD IXb
PHKG2 GSD IXc
PYGL GSD VI    (Hers disease)
PYGM GSD V  (McArdle disease)
RBCK1 Polyglucosan body myopathy 1 with or without immunodeficiency
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.

There are broad phenotypic classes of GSD and they are generally categorized as hepatic GSD or muscular GSDs. Hepatic GSDs are characterized by recurrent hypoglycemia due to the inability to release glucose into the bloodstream during times of fasting, and acquired hepatomegaly secondary to glycogen accumulation in the liver. Muscular GSDs are characterized by exercise intolerance, myopathies and/or myalgias due to muscle tissue breakdown from compromised energy production. Additionally, the kidneys, heart and central nervous system can also be affected. 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 GSDs, in the form of continual carbohydrate supply is available for some of the GSDs and functions to prevent use of the endogenous glycogen pathway. Hepatic glycogen storage diseases have also been treated with liver transplant. Enzyme replacement therapy is commercially available for GSD II; which is a lysosomal storage disease.

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

The glycogen storage diseases are individually rare, with incidences ranging from 1:14,000 – 1:800,000. Certain ethnicities may have a higher prevalence of specific glycogen storage diseases.

This test is appropriate for any individual with any combination of clinical features consistent with a GSD including: recurrent hypoglycemia with or without hepatomegaly, or individuals with exercise intolerance, myalgias and or myopathies; especially when associated with rhabdomyolysis.

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, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

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
ACADM NM_000016.5
ACADS NM_000017.3
ACADSB NM_001609.3
ACADVL NM_000018.3
AGL NM_000642.2
ALDOA NM_000034.3
CPT1A NM_001876.3
CPT2 NM_000098.2
ENO3 NM_053013.3
ETFA NM_000126.3
ETFB NM_001985.2
ETFDH NM_004453.3
FBP1 NM_000507.3
G6PC NM_000151.3
GAA* NM_000152.3
GBE1 NM_000158.3
GYG1 NM_004130.3
GYS1 NM_002103.4
GYS2 NM_021957.3
HADH NM_005327.4
HADHA NM_000182.4
HADHB NM_000183.2
HMGCL NM_000191.2
HMGCS2 NM_005518.3
LAMP2 NM_002294.2
LDHA NM_005566.3
MLYCD NM_012213.2
NADK2 NM_001085411.2
PFKM NM_000289.5
PGAM2 NM_000290.3
PGM1 NM_002633.2
PHKA1 NM_002637.3
PHKA2 NM_000292.2
PHKB NM_000293.2; NM_001031835.2
PHKG2 NM_000294.2
POLG NM_002693.2
PYGL NM_002863.4
PYGM NM_005609.3
RBCK1 NM_031229.3
SLC22A5 NM_003060.3
SLC25A20 NM_000387.5
SLC2A2 NM_000340.1
SLC37A4 NM_001164277.1
SLC52A1 NM_017986.3
SLC52A2 NM_024531.4
SLC52A3 NM_033409.3

GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.