Glycogen storage disease type 1a and 1b
Glycogen storage disease type 1a and 1b (also known as von Gierke disease) can be clinically indistinguishable. Pathogenic variants in G6PC or SLC37A4 lead to autosomal recessive glycogen storage disease types 1a or 1b, respectively (GSD I). G6PC encodes for glucose-6-phosphatase, which catalyzes the terminal step of gluconeogenesis and glycogenolysis. SLC37A4 encodes for glucose-6-phosphate transporter into endoplasmic reticulum, where G6PC catalyzes the next step. The incidence of GSD I is 1 in 100,000. GSD I may have neonatal onset, but typically presents at 3-4 months of age with hypoglycemia. Additional features can include hepatomegaly, renomegaly, growth retardation, osteopenia, round face, epistaxis, delayed puberty, and polycystic ovaries. GSD type 1b can also cause infections and inflammatory bowel disease due to neutropenia/neutrophil dysfunction.
• Hepatomegaly and renomegaly
• Elevated levels of lactate, fats and uric acid in blood
• Delayed growth and delayed puberty
• Bone thinning from osteoporosis
• Increased mouth ulcers and infections
PCR-based sequencing of entire coding region, intron/exon boundaries, as well as known pathogenic variants (HGMD 2017.3) in the promoter and deep intronic regions of the specified gene(s).
Sensitivity and Limitations
The analytical sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed. Variants in regulatory regions and non-reported variants in untranslated regions may not be detected by this test. Large deletions/ duplications, large insertions and other complex genetic events will not be identified using sequencing methodology.
How to Order
Testing for these genes also available as part of the Metaboseq panel by next-generation sequencing. Deletion/duplication analysis and targeted variant analysis is also available for these genes. Download Inborn Errors of Metabolism requisition.
Bali DS, Chen YT, Austin S, et al. Glycogen Storage Disease Type I. 2006 Apr 19 [Updated 2016 Aug 25]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1312/
Chou, JY and Mansfield, BC. (1999) Molecular genetics of type 1 glycogen storage diseases. Trends Endocr. Metab. 10: 104-113.
Lei, KJ, Shelly, LL, et al. (1993) Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a. Science. 262(5133):580-3.
Parikh, NS, and Ahlawat, R. Glycogen Storage Disease Type I (Von Gierke Disease). StatPearls [Internet].