# Glycogen storage diseases
A glycogen storage disease (GSD) is an inherited metabolic disorder in which a defective enzyme or transporter disrupts the synthesis or breakdown of glycogen, the branched glucose polymer that serves as the body's main store of quickly mobilized carbohydrate energy. The result is either an inability to release glucose when it is needed, as in the liver-focused types, or an accumulation of abnormal or excess glycogen in tissues, most often liver and muscle. The hepatic GSDs are classified as inborn errors of metabolism caused by abnormalities of the enzymes that catalyze the synthesis or degradation of glycogen, and at least 16 recognized types are now described since von Gierke disease was reported by Edgar von Gierke in 1929.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/)
| Key fact | Detail |
|---|---|
| Definition | Inherited disorders of the enzymes that synthesize or degrade glycogen; at least 16 recognized types[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) |
| First description | Von Gierke disease (GSD Ia), described in 1929 from autopsies showing excess glycogen in the livers and kidneys of two patients[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC10354582/) |
| Frequency of GSD I | Overall incidence 1 in 100,000 individuals; GSDIa accounts for 80 percent of GSDI cases[3](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-i/) |
| Inheritance | Autosomal recessive for the types described in the sources, including GSD 0, GSD I, and GSD V[3](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-i/) • [4](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-0/) • [5](https://www.ncbi.nlm.nih.gov/books/NBK1344/) |
| Mainstay of treatment | Nutritional therapy, primarily for the past 50 years; cornstarch dosing maintains blood glucose in hepatic types[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) • [6](https://sagsd.org/wp-content/uploads/2022/11/Type-6-9.pdf) |
| First gene therapy | Genglycos (pariglasgene brecaparvovec-opnr), an AAV8 gene therapy for GSDIa, received FDA accelerated approval on August 19, 2026[7](https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-aged-8-years-and-older-glycogen-storage-disease-type-ia) |
## Classification and genetic basis
Each type is defined by the enzyme or transporter that is deficient and by the tissue where the defect matters most. The numbered scheme reflects the order in which the biochemical defects were identified, and several types carry eponyms from the physicians who first described them.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/)
| Type | Name | Defective gene and product | Chromosome | Year described |
|---|---|---|---|---|
| 0 | Glycogen synthase deficiency | GYS2 (liver glycogen synthase) | 12 (12p12.1) | 1963[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) |
| Ia | Von Gierke disease | G6PC (glucose-6-phosphatase) | 17 (17q21.31) | 1929[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) |
| Ib | Transport defect | SLC37A4 (glucose-6-phosphate transporter) | 11 (11q23.3) | 1978[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) |
| II | Pompe disease | GAA (acid alpha-glucosidase) | 17 (17q25.3) | 1932[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) |
| IIIa / IIIb | Forbes or Cori disease | AGL (glycogen debranching enzyme; IIIb liver only) | 1 (1p21.2) | 1928[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) |
| V | McArdle disease | PYGM (muscle glycogen phosphorylase) | 11 (11q13.1) | 1951[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) |
The two major subtypes of GSD I illustrate how one clinical picture can arise from two molecular defects. Glucose-6-phosphatase and its transporter function as a multicomponent system: the transporter moves glucose 6-phosphate into the endoplasmic reticulum, where the enzyme converts it to free glucose. Deficiency of either component blocks the terminal step of both [glycogenolysis](https://www.edgepedia.org/glycogenolysis) and gluconeogenesis, so the liver cannot release glucose during fasting.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC10354582/) Variants in G6PC1 cause GSDIa and variants in SLC37A4 cause GSDIb; glucose 6-phosphate that cannot be broken down is instead converted to glycogen and fat, which accumulate toxically in liver and kidney cells.[3](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-i/)
## Clinical pictures by affected tissue
**Liver types.** In GSD I, signs typically appear around age 3 or 4 months, when babies begin sleeping through the night and fasting longer. Affected infants develop hypoglycemia, which can cause seizures, along with lactic acidosis, hyperuricemia, and hyperlipidemia; an enlarged liver gives a protruding abdomen, and teens and adults may develop liver adenomas, usually benign but occasionally malignant.[3](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-i/) GSDIb adds neutropenia, usually apparent by age 1, with recurrent bacterial infections, inflammatory bowel disease, and oral problems; these features are specific to GSDIb and typically not seen in GSDIa.[3](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-i/) GSD VI and IX present with hepatomegaly and hypoglycemia, and their nutrition therapy aims to prevent the primary manifestations of hypoglycemia, ketosis, and hepatomegaly and the secondary complications of short stature, delayed puberty, and cirrhosis.[6](https://sagsd.org/wp-content/uploads/2022/11/Type-6-9.pdf)
**Muscle types.** GSD V (McArdle disease) results from deficiency of myophosphorylase, the muscle isoenzyme of glycogen phosphorylase (E.C. 2.4.1.1); in affected individuals residual enzyme activity is virtually undetectable, and the condition is inherited in an autosomal recessive manner.[5](https://www.ncbi.nlm.nih.gov/books/NBK1344/) [Pompe disease](https://www.edgepedia.org/glycogen-storage-disease-type-ii) (GSD II) is caused by absence or deficiency of acid alpha-glucosidase, a lysosomal enzyme that cleaves the α-1,4- and α-1,6-glycosidic bonds of glycogen to glucose; glycogen therefore accumulates within lysosomes, and in the classical infantile form progressive lysosomal filling destroys the contractile elements of muscle cells.[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC4135233/)
**Synthesis failure.** GSD 0 differs from the other types in that glycogen cannot be formed at all rather than accumulating. In muscle GSD 0, caused by GYS1 variants, affected individuals have muscle pain and weakness or fainting after moderate activity such as climbing stairs, and the condition impairs the heart's ability to pump blood, increasing the risk of cardiac arrest and sudden death particularly after physical activity; some also have long QT syndrome. Liver GSD 0 is caused by GYS2 variants.[4](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-0/)
## Diagnosis
Diagnosis has shifted from tissue biochemistry toward DNA analysis. For the liver GSDs, the [American College of Medical Genetics](https://www.edgepedia.org/american-college-of-medical-genetics) and Genomics practice resource states that diagnosis by DNA analysis is preferable to liver biopsy so that patients can avoid an invasive procedure; next-generation sequencing panels covering known liver GSDs and disorders of fructose metabolism help distinguish conditions with similar presentations, and exome sequencing is increasingly used. Limitations remain: deletions and duplications can be missed on exome sequencing, and variants of uncertain significance may require follow-up with histology and enzyme testing on a liver biopsy specimen.[9](https://www.nature.com/articles/s41436-018-0364-2)
For GSD V, options include single-gene testing of PYGM, where sequence analysis detects 99 percent of pathogenic variants, or a metabolic myopathy multigene panel; enzyme assay of myophosphorylase activity in a muscle biopsy or homogenate is also diagnostic.[5](https://www.ncbi.nlm.nih.gov/books/NBK1344/) For GSD IV, prenatal testing is possible by measuring glycogen branching enzyme activity in amniocytes or cultured chorionic villi.[10](https://www.ncbi.nlm.nih.gov/sites/books/NBK115333/pdf/Bookshelf_NBK115333.pdf)
## Management
**Dietary therapy.** Nutritional therapy has remained the primary treatment for the GSDs over the past 50 years. For hepatic types such as VI and IX, the goal is to maintain normal blood glucose and ketone concentrations using appropriate amounts of cornstarch, which releases glucose slowly; cornstarch may not be well tolerated in infants before about 12 months of age because amylase may not be fully functional. High-protein diets may help by supplying gluconeogenic precursors, serving as direct muscle fuel, and reducing glycogen storage.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/) • [6](https://sagsd.org/wp-content/uploads/2022/11/Type-6-9.pdf) [Continuous glucose monitoring](https://www.edgepedia.org/continuous-glucose-monitoring) is increasingly used in hepatic GSDs to keep patients in euglycemia and is becoming a key endpoint in gene therapy studies.[11](https://onlinelibrary.wiley.com/doi/10.1002/edm2.70274)
**Enzyme and gene therapy.** Pompe disease is treated with enzyme replacement therapy using recombinant human GAA (alglucosidase alpha, Myozyme), a 110 kDa precursor with mannose-6-phosphate groups that bind cell-surface receptors.[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC4135233/) For GSDIa, the FDA granted accelerated approval on August 19, 2026, to Genglycos (pariglasgene brecaparvovec-opnr), a one-time AAV8-based gene therapy that delivers a functional G6PC gene to the liver; it is indicated to reduce daily cornstarch intake as an adjunct to nutritional management in patients 8 years of age and older, and it is the first approved treatment for the condition.[7](https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-aged-8-years-and-older-glycogen-storage-disease-type-ia) In the pivotal Phase 3 trial, 46 patients were randomized 1:1 to a single intravenous dose of 1.0 × 1013 genome copies per kilogram or placebo; at week 48 the treated group had a statistically significant 30.9 percent greater reduction in daily cornstarch intake than placebo and reduced their daily cornstarch doses by about one per day. Treated patients had numerically higher rates of hypoglycemia, elevated lactate, hyperglycemia, and hypertriglyceridemia (29 percent versus 8 percent for triglycerides), suggesting restored liver G6Pase activity may not have fully compensated for reduced cornstarch intake in all patients; continued approval is contingent on verification of clinical benefit in confirmatory trials.[12](https://www.fda.gov/media/194583/download?attachment=) [Gene therapy](https://www.edgepedia.org/gene-therapy) programs for other GSD types are in development, with rAAV-mediated treatment for GSD Ia having entered Phase 3 trials as of 2023.[13](https://www.cellmolbiol.org/index.php/CMB/article/download/5911/3711/12235)
## References
1. [Dietary Management of the Glycogen Storage Diseases: Evolution of Treatment and Ongoing Controversies, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7442342/)
2. [Glycogen storage diseases: An update, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC10354582/)
3. [Glycogen storage disease type I, MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-i/)
4. [Glycogen storage disease type 0, MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-0/)
5. [Glycogen Storage Disease Type V, GeneReviews, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK1344/)
6. [Diagnosis and management of glycogen storage diseases type VI and IX, ACMG clinical practice resource (PDF)](https://sagsd.org/wp-content/uploads/2022/11/Type-6-9.pdf)
7. [FDA Approves First Therapy for Patients aged 8 years and older with Glycogen Storage Disease Type Ia, FDA News Release](https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-aged-8-years-and-older-glycogen-storage-disease-type-ia)
8. [Pompe disease: from pathophysiology to therapy and back again, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4135233/)
9. [Diagnosis and management of glycogen storage diseases type VI and IX, Genetics in Medicine](https://www.nature.com/articles/s41436-018-0364-2)
10. [Glycogen Storage Disease Type IV, GeneReviews PDF, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/sites/books/NBK115333/pdf/Bookshelf_NBK115333.pdf)
11. [Continuous Glucose Monitoring in Glycogen Storage Diseases: A Systematic Review, Endocrinology, Diabetes & Metabolism](https://onlinelibrary.wiley.com/doi/10.1002/edm2.70274)
12. [August 19, 2026 Summary Basis for Regulatory Action, GENGLYCOS, FDA](https://www.fda.gov/media/194583/download?attachment=)
13. [GSD update, Cell. Mol. Biol. 2025, 71(11): 8-19](https://www.cellmolbiol.org/index.php/CMB/article/download/5911/3711/12235)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Digestive, metabolic, and endocrine conditions › Inherited and other metabolic disorders*
*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 21, 2026 · Edited: Sep 30, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license