Glycogen Storage Disease (GSD) and Disorders of Glucose Metabolism Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10385 AGL 81407,81479 Order Options and Pricing
ALDOA 81479,81479
ALDOB 81479,81479
ENO3 81479,81479
EPM2A 81404,81479
FBP1 81479,81479
G6PC1 81479,81479
GAA 81406,81479
GBE1 81479,81479
GYG1 81479,81479
GYS1 81479,81479
GYS2 81479,81479
LAMP2 81405,81479
LDHA 81479,81479
NHLRC1 81403,81479
PC 81406,81479
PCK1 81479,81479
PCK2 81479,81479
PFKM 81479,81479
PGAM2 81479,81479
PGM1 81479,81479
PHKA1 81479,81479
PHKA2 81479,81479
PHKB 81479,81479
PHKG2 81479,81479
PRKAG2 81406,81479
PRKAG3 81479,81479
PYGL 81479,81479
PYGM 81406,81479
RBCK1 81479,81479
SLC16A1 81479,81479
SLC2A2 81479,81479
SLC37A4 81406,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10385Genes x (33)81479 81403, 81404, 81405, 81406, 81407, 81479 $1030 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

The Glycogen Storage Diseases (GSDs) are a group of inherited metabolic disorders that result from a defect in any one of several enzymes required for either glycogen synthesis or glycogen degradation. Broadly speaking, the GSDs can be divided into hepatic or myopathic forms. Patients with hepatic GSDs typically present with hypoglycemia and often with hepatomegaly, whereas those with myopathic forms of GSDs can present with exercise intolerance, muscle pain, rhabdomyolysis and/or muscle weakness. Some of the myopathic forms of GSD can present with cardiomyopathy as well. When performed, liver or muscle biopsies may reveal an accumulation of glycogen or abnormally structured glycogen, dependent upon the specific enzymatic defect. Additional long-term complications are common in many of the GSDs. The severity of the GSDs range from those that are fatal in infancy if untreated to mild disorders with a normal lifespan. While some forms of GSD affect a single tissue type (for example, skeletal muscle in McArdle disease), other GSDs affect multiple systems.

Defects in a number of genes that encode proteins involved in glucose or fructose metabolism can result in a clinical picture similar to that of some of the GSDs, and are therefore included in this sequencing panel.

Defects in the following genes are associated primarily with a hepatic clinical presentation:

GYS2 (GSD 0, liver type); G6PC1/G6PC (GSD Ia, von Gierke Disease); SLC37A4 (GSD Ib); PYGL (GSD VI, Hers Disease); PHKA2 (GSD IXa); PHKG2 (GSD IXc); SLC2A2 (GSD XI*, Fanconi-Bickel Disease); ALDOB (Hereditary Fructose Intolerance); FBP1 (fructose-1,6-bisphosphatase deficiency); SLC16A1 (MCT1 Deficiency); EPM2A** (progressive myoclonic epilepsy 2A); NHLRC1** (progressive myoclonic epilepsy 2B)

Defects in the following genes are associated primarily with a myopathic clinical presentation (may include cardiac defects):

GYS1 (GSD 0, muscle type); GAA (GSD II, Pompe Disease); PYGM (GSD V, McArdle Disease); PFKM (GSD VII, Tarui Disease); PHKA1 (GSD IXd); PGAM2 (GSD X); LDHA (GSD XI*); ENO3 (GSD XIII); GYG1 (GSD XV); LAMP2 (Pseudoglycogenosis II, Danon Disease); PRKAG3 (altered glycogen and triglyceride levels in muscle)

Defects in the following genes are associated with both a hepatic and/or a myopathic clinical presentation (may include cardiac defects):

AGL (GSD III, Cori Disease); GBE1 (GSD IV, Andersen Disease, Adult Polyglucosan Body Disease); PHKB (GSD IXb); ALDOA (GSD XII); PGM1 (GSD XIV); PRKAG2 (GSD of the heart, congenital); PC (Pyruvate Carboxylase Deficiency); PCK1 (PEP Carboxykinase Deficiency, cytosolic); PCK2 (PEP Carboxykinase Deficiency, mitochondrial); RBCK1 (polyglucosan body myopathy 1 with or without immunodeficiency)

* Defects in both the GLUT2 transporter and lactate dehydrogenase have been named GSD XI, although these are distinct disorders.

** The EPM2A and NHLRC1 genes are primarily associated with progressive myoclonic epilepsy, although hepatic failure can occur. In both disorders, intracellular polyglucosan bodies can be found in various tissues.

Many of the glycogen storage diseases are reviewed individually in GeneReviews. In addition, comprehensive reviews of the hepatic forms of GSD (Wolfsdorf and Weinstein 2003. PubMed ID: 12618563; Burda and Hochuli 2015. PubMed ID: 26001652) as well as the myopathic forms of GSD (DiMauro and Spiegel 2011. PubMed ID: 22106711; Scalco et al. 2015. PubMed ID: 25929793) are available. Additional comprehensive reviews of all glycogen storage diseases are also available (Hicks et al. 2011. PubMed ID: 21910565; Kilimann and Oldfors 2015. PubMed ID: 25376534; Adeva-Andany et al. 2016. PubMed ID: 27051594; Cenacchi et al. 2019. PubMed ID: 31363843). The GSDs have traditionally been diagnosed using a combination of clinical symptoms, biochemical results, and pathology findings. Within the last decade, DNA sequence variant analysis has become the primary method for diagnosing the glycogen storage diseases.

The estimated disease incidence for all forms of glycogen storage disease in the United States is approximately 1 in 20,000 to 1 in 43,000 births (Ozen. 2007. PubMed ID: 17552001). These disorders are found in all ethnic groups, but founder pathogenic variants may put certain populations at higher risk (for example, GSD Type III in the Faroe Islands and GSD Type VI in the U.S. Mennonite community) (Santer et al. 2001. PubMed ID: 11378828; Chang et al. 1998. PubMed ID: 9536091).

Obtaining an accurate molecular diagnosis may help in determining the patient’s prognosis, planning for the best treatment and/or management of symptoms, and allow for reproductive planning.

Genetics

Although the majority of disorders tested for in this sequencing panel show autosomal recessive inheritance, a few exceptions do exist. Two forms of GSD Type IX (due to pathogenic variants in PHKA1 and PHKA2) as well as pseudoglycogenosis II (Danon Disease, caused by pathogenic variants in LAMP2) show X-linked recessive inheritance. Female carriers of PHKA2 pathogenic variants may or may not be affected, depending on the pattern of X-chromosome inactivation. To date, no symptomatic females with PHKA1 variants have been reported (Herbert et al. 2018. PubMed ID: 21634085). Female carriers of LAMP2 variants tend to be more mildly affected than males (Cenacchi et al. 2019. PubMed ID: 31363843). MCT1 deficiency (due to pathogenic variants in SLC16A1) appears to be inherited in both an autosomal recessive and autosomal dominant manner, with patients with two variants being more severely affected (van Hasselt et al. 2014. PubMed ID: 25390740). Glycogen storage disease of the heart (due to pathogenic variants in PRKAG2) is inherited in an autosomal dominant manner.

All manner of single nucleotide and small sequence variants (missense, nonsense, splicing, small deletions, small insertions or duplications, and small indels) have been reported in the genes in this panel. Larger copy number variants (particularly deletions) have also been reported in a number of the genes in this panel (AGL, EPM2A, FBP1, G6PC1, GAA, GBE1, LAMP2, PC, PHKA2, PHKB, PYGL, PYGM, and SLC37A4). To our knowledge, de novo variants are not a common cause of disease for the genes in this panel.

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Due to the genetic heterogeneity of the disorders tested in this panel, the clinical sensitivity of this specific grouping of genes is difficult to estimate. To our knowledge, only two studies have been published in which multiple genes known to cause a glycogen storage disease were sequenced via NextGen sequencing. In the first study (Wang et al. 2013. PubMed ID: 22899091), 16 genes were examined. The authors reported a confirmed molecular diagnosis in 11 of 17 patients (~65%) that were suspected to have a GSD. In the second study (Vega et al. 2016. PubMed ID: 26913919), 19 out of 43 patients (~44%) were found to harbor pathogenic variants in genes included in our sequencing panel, and 4 in non-GSD genes which are not included in our panel. Of note, our panel contains several genes that were not reported by either Wang (2013) or Vega 2016): EPM2A, FBP1, LAMP2, NHLRC1, PC, PCK1, PCK2, PRKAG2, PRKAG3, RBCK1, and SLC16A1.

The sensitivity of this panel will vary based on the clinical phenotype of the patient. Analytical sensitivity of this test is expected to be high as the majority of pathogenic variants reported in the genes in the panel are detectable via direct sequencing.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.9% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Genetic testing for Glycogen Storage Diseases (GSDs) and disorders of glucose metabolism with a similar clinical presentation to the GSDs is available for patients suspected to be affected with one of these disorders.

Diseases

Name Inheritance OMIM ID
Congenital Disorder of Glycosylation Type It AR 614921
Danon Disease XL 300257
Fanconi-Bickel Syndrome AR 227810
Fructose-Biphosphatase Deficiency AR 229700
Glycogen Storage Disease 0, Liver AR 240600
Glycogen Storage Disease 0, Muscle AR 611556
Glycogen Storage Disease Of Heart, Lethal Congenital AR 261740
Glycogen Storage Disease Type Ia AR 232200
Glycogen Storage Disease Type Ib AR 232220
Glycogen Storage Disease Type Ic AR 232240
Glycogen Storage Disease Type II AR 232300
Glycogen Storage Disease Type III AR 232400
Glycogen Storage Disease Type IV AR 232500
Glycogen Storage Disease Type IXa1 XL 306000
Glycogen Storage Disease Type IXc AR 613027
Glycogen Storage Disease Type IXd XL 300559
Glycogen Storage Disease Type V AR 232600
Glycogen Storage Disease Type VI AR 232700
Glycogen Storage Disease Type VII AR 232800
Glycogen Storage Disease Type X AR 261670
Glycogen Storage Disease Type XI AR 612933
Glycogen Storage Disease Type XII AR 611881
Glycogen Storage Disease Type XIII AR 612932
Glycogen Storage Disease Type XV AR 613507
Glycogen Storage DiseaseType IXb AR 261750
Hereditary Fructose Intolerance AR 229600
Lafora Disease AR 254780
Monocarboxylate Transporter 1 Deficiency AD,AR 616095
Phosphoenolpyruvate Carboxykinase Deficiency, Cytosolic AR 261680
Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial AR 261650
Polyglucosan body disease, adult form AR 263570
Polyglucosan Body Myopathy 1 with or without Immunodeficiency AR 615895
Polyglucosan Body Myopathy 2 AR 616199
Pyruvate Carboxylase Deficiency AR 266150

Related Test

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PGxome®

Citations

  • Adeva-Andany et al. 2016. PubMed ID: 27051594
  • Burda and Hochuli 2015. PubMed ID: 26001652
  • Cenacchi et al. 2019. PubMed ID: 31363843
  • Chang et al. 1998. PubMed ID: 9536091
  • DiMauro and Spiegel 2011. PubMed ID: 22106711
  • Herbert et al. 2018. PubMed ID: 21634085
  • Hicks et al. 2011. PubMed ID: 21910565
  • Kilimann and Oldfors 2015. PubMed ID: 25376534
  • Ozen. 2007. PubMed ID: 17552001
  • Santer et al. 2001. PubMed ID: 11378828
  • Scalco et al. 2015. PubMed ID: 25929793
  • van Hasselt et al. 2014. PubMed ID: 25390740
  • Vega et al. 2016. PubMed ID: 26913919
  • Wang et al. 2013. PubMed ID: 22899091
  • Wolfsdorf and Weinstein 2003. PubMed ID: 12618563

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

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