Glycogen Storage Disease Types 1A & 1B
Glycogen Storage Disease Type I, also called von Gierke disease, is an autosomal recessive metabolic disorder in which glycogen accumulates in the liver and kidneys, and glucose production during fasting is impaired.
PrintGlycogen Storage Disease Type I, also called von Gierke disease, is an autosomal recessive metabolic disorder in which glycogen accumulates in the liver and kidneys, and glucose production during fasting is impaired.
Two disease subtypes exist. Glycogen Storage Disease Type Ia (GSDIa) is caused by mutations of the glucose-6-phosphatase gene G6PC and accounts for approximately 80% of Type I. Mutations in the glucose-6-phosphate translocase gene SLC37A4 cause Glycogen Storage Disease Type Ib (GSDIb) and account for approximately 20% of Type I. The former “non-a” disease types are now generally considered to be Type Ib.
The Gene Sequence Analysis tests for each disease type, Ia and Ib, are performed separately. Approximately 99% of G6PC mutations and 98% of SLC37A4 mutations are detectable. They may be run simultaneously or in sequence as requested by the ordering physician. Genetic Testing for GSDIa and GSDIb is useful for differentiating from several other metabolic diseases with similar presentations, as a non-invasive diagnostic option to liver biopsy, and for carrier detection.
The Ambry Test: Glycogen Storage Disease Type Ia is a Gene Sequencing Analysis test that detects approximately 99% of G6PC mutations and is appropriate for carrier or diagnostic testing. The Ambry Test: Glycogen Storage Disease Type Ib is a gene sequence analysis test that detects approximately 98% of SLC37A4 mutations, and is appropriate for carrier or diagnostic testing. Specific mutation analysis for a known familial mutation in G6PC or SLC37A4 is also available.
Glycogen storage disease type I, also called von Gierke disease, is an autosomal recessive metabolic disorder in which glycogen accumulates in the liver and kidneys and glucose production during fasting is impaired. The incidence is approximately 1/100,000.Two disease subtypes exist and are caused by genetic defects in different components of an enzyme complex that regulates glycogen breakdown in the kidneys and liver to maintain the blood glucose level. Type Ia (GSDIa) is caused by mutations of the glucose-6-phosphatase gene G6PC (also called G6Pase) and accounts for approximately 80% of type I. Mutations in the glucose-6-phosphate translocase gene SLC37A4 (also called G6PT1) cause type Ib and account for approximately 20% of type I.1 The former “non-a” disease types are now generally considered to be type Ib.2,3 Genotype does not correlate well with phenotype in these variable conditions.1,4 GSDI occurs in many ethnic groups and some mutations are frequent in patients of specific ethnicities. A G6PC mutation p.R83C is carried by approximately 1/71 Ashkenazi Jewish people, putting members of that group at increased risk for a child with GSDIa.5
Affected children often present at age three or four months with hypoglycemic seizures. Other symptoms that develop are enlarged liver and kidneys, characteristic facial features, thin limbs, short stature, lactic acidosis, and elevated blood lipids and uric acid. Long term complications are osteoporosis, kidney disease, pulmonary hypertension, gout, hepatic adenoma, pancreatitis, and polycystic ovaries in females.Type Ib usually includes additional features of neutropenia and impaired function of platelets, neutrophils, and monocytes. This can cause nosebleeds, oral ulcers, Crohn’s-like intestinal disease, and recurrent bacterial infections. Dietary treatment can restore near normal growth and puberty, and many patients live well into adulthood.
Genetic testing is useful for differentiating GSDIa and GSDIb from several other metabolic diseases with similar presentations, as a non-invasive diagnostic option to liver biopsy,6 and for carrier detection.
Tests for each disease type are performed separately. They may be run simultaneously or in sequence as requested by the ordering physician. These Ambry Tests are full gene sequence analyses performed by PCRbased double-stranded automated sequencing in the sense and antisense directions for exons 1-5 of the G6PC gene or exons 1-8 of the SLC37A4 gene, plus at least 20 bases into the 5’ and 3’ ends of all the related introns. Specific mutation analysis for individual G6PC or SLC37A4 mutations known to be in the family is also available.
Approximately 99% of G6PC mutations in GSDIa and 98% of SLC37A4 mutations in GSDIb are detectable by these tests.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique |
|---|---|
| 1880 | G6PC Gene Sequence Analysis |
| 1900 | SLC37A4 Gene Sequence Analysis |
| Technique | Days |
|---|---|
| G6PC Gene Sequence Analysis | 20-42 |
| SLC37A4 Gene Sequence Analysis | 20-42 |
1. Reviewed in Chou JY and Mansfield BC. Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. Hum Mutation. 2008;29:921-930. [PMID: 18449899]
2. Veiga-da-Cunha M, Gerin I, et al. The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. Eur J Hum Genet. 1999;7:717-723. [PMID: 10482962]
3. Janecke AR, Lindner M, et al. Mutation analysis in glycogen storage disease type 1 non-a. Hum Genet. 2000;107:285-289. [PMID: 11071391]
4. Melis D, Fulceri R, et al. Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature. Eur J Pediatr. 2005;164:501-508. [PMID: 15906092]
5. Ekstein J, Rubin BY, et al. Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population. Am J Med Genet. 2004;129A;162-164. [PMID: 15316959]
6. Rake JP, ten Berge AM, et al. Glycogen storage disease type Ia: recent experience with mutation analysis, a summary of mutations reported in the literature and a newly developed diagnostic flow chart. Eur J Pediatr. 2000;159:322-330. [PMID: 10834516]