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  • Test code: 06158
  • 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 Muscle Glycogen Storage Disease Panel

Test description

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

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Primary panel (14 genes)

ALDOA ENO3 GAA GBE1 GYG1 GYS1 LAMP2 LDHA PFKM PGAM2 PHKA1 PHKB PYGM RBCK1

Add-on fatty acid oxidation genes (21 genes)

There is significant clinical overlap between the myopathy observed in patients with late onset fatty acid oxidation disorders and some of the muscular glycogen storage diseases. If clinically appropriate, these genes can be added at no additional charge.

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)

There is significant clinical overlap between the myopathy observed in PGM1-related conditions, POLG-related conditions and some of the muscular glycogen storage diseases. If clinically appropriate, these genes can be added at no additional charge.

PGM1 POLG

Alternative tests to consider

For a broader analysis of the genetics of glycogen storage disorders:

Gene Disorder
ALDOA GSD XII, Aldolase A deficiency
ENO3 GSD 13
GAA GSD II (Pompe disease)
GBE1 GSD IV
GYG1 GSD XV
GYS1 GSD 0 (Glycogen synthase, muscle 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)
PHKB GSD IXb   
PYGM GSD V  (McArdle disease)
RBCK1 Polyglucosan body myopathy 1 with or without immunodeficiency

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.

Muscular GSDs are characterized by exercise intolerance, myopathies and/or myalgias due to muscle tissue breakdown secondary to compromised energy production. Significant muscle breakdown can lead to myoglobinuria, and if untreated, myoglobinuria can cause kidney failure. 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 frequent carbohydrate dosing is available for some of the GSDs and functions to prevent the use of the endogenous glycogen catabolic pathway. Enzyme replacement therapy is commercially available for GSD II, a lysosomal storage disorder.

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 averaging around 1:100,000. Certain ethnicities may have a higher prevalence of specific glycogen storage diseases.

GSD II 1:14,000 in African-Americans to 1:50,000 in Taiwan and 1:600,000 in Portugal.

This test is appropriate for any individual with any combination of clinical features consistent with a muscular GSD including recurrent, unexplained episodes of muscle cramping, myalgias and myopathy without concurrent 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
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
GAA* NM_000152.3
GBE1 NM_000158.3
GYG1 NM_004130.3
GYS1 NM_002103.4
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
PHKB NM_000293.2; NM_001031835.2
POLG NM_002693.2
PYGM NM_005609.3
RBCK1 NM_031229.3
SLC22A5 NM_003060.3
SLC25A20 NM_000387.5
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.