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A glycogen storage disease characterized by muscle and heart glycogen deficiency. It has been described in three siblings (two brothers and their younger sister). The older brother died at 10.5 years of age as a result of sudden cardiac arrest and the younger brother presented with hypertrophic cardiomyopathy, abnormal heart rate and blood pressure during exercise, and muscle fatigability. The sister showed no symptoms but a lack of glycogen was identified through muscle biopsy. The syndrome is caused by homozygous missense mutations in the gene encoding muscle glycogen synthase.
Features include: Bilateral tonic-clonic seizure, Stroke, Left atrial enlargement, and Thickened left heart wall (left ventricular hypertrophy) and 3 more.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Heart and blood vessels | 4 | Stroke, Left atrial enlargement, Thickened left heart wall (left ventricular hypertrophy) |
Brain and nerves | 3 | Bilateral tonic-clonic seizure, Stroke, Exercise intolerance |
Muscles | 1 | Decreased muscle glycogen content |
GYS1 encodes glycogen synthase 1 (737 aa). Glycogen synthase participates in the glycogen biosynthetic process along with glycogenin and glycogen branching enzyme. Highest expression in Muscle Skeletal (167.7 TPM) and Cells Cultured fibroblasts (85.8 TPM).
Glycogen storage disease due to muscle and heart glycogen synthase deficiency is caused by mutations in the GYS1 gene on chromosome 19.
The GYS1 protein participates in GYS1 catalyzes the polyglucosylation of oligoGlc-GYG1 and GYS1 catalyzes the incorporation of phosphoglucose into glycogen-GYG1 pathways.
GYS1 is classified as a druggable target (Enzyme category) with score 52.2.
Genetic testing for GYS1 is available. Testing is considered confirmatory for diagnosis.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
1 clinical trial registered, 1 recruiting. Interventions under study include other interventions. Research is primarily sponsored by academic and government institutions.
9 publications have been identified in PubMed for glycogen storage disease due to muscle and heart glycogen synthase deficiency. Research spans Review / Meta-Analysis (33%), Basic Science / Preclinical (22%), and Gene Therapy / Novel Therapeutics (22%).
Holt BD (2025). [PMID: 39604266](https://pubmed.ncbi.nlm.nih.gov/39604266/). *Mol Ther*. [Gene Therapy / Novel Therapeutics]
Llauradó A (2025). [PMID: 40398079](https://pubmed.ncbi.nlm.nih.gov/40398079/). *Mol Genet Metab*. [Case Report / Case Series]
Weiss L (2025). [PMID: 40268518](https://pubmed.ncbi.nlm.nih.gov/40268518/). *Clin Transl Med*. [Gene Therapy / Novel Therapeutics]
Chen J (2024). [PMID: 38803914](https://pubmed.ncbi.nlm.nih.gov/38803914/). *Heliyon*. [Basic Science / Preclinical]
Mishra K (2024). [PMID: 39334863](https://pubmed.ncbi.nlm.nih.gov/39334863/). *Biomolecules*. [Review / Meta-Analysis]
Gaspar RC (2024). [PMID: 39171753](https://pubmed.ncbi.nlm.nih.gov/39171753/). *Am J Physiol Endocrinol Metab*. [Basic Science / Preclinical]
Colpaert M (2024). [PMID: 39277505](https://pubmed.ncbi.nlm.nih.gov/39277505/). *Neurotherapeutics*. [Review / Meta-Analysis]
Koch RL (2024). [PMID: 39817232](https://pubmed.ncbi.nlm.nih.gov/39817232/). *Ann Transl Med*. [Other]
Parenti G (2024). [PMID: 39482698](https://pubmed.ncbi.nlm.nih.gov/39482698/). *Orphanet J Rare Dis*. [Review / Meta-Analysis]
Data assembled from 8 of 12 sources · Last updated Sep 21, 2026, 4:52 AM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center