GYS1 gene
Also known as: Glycogen storage disease due to muscle and heart glycogen synthase deficiency, GSD 0b
OMIM#611556 https://omim.org/entry/611556
1. The Disease:
Glycogen storage disease due to muscle and heart glycogen synthase deficiency is characterised by muscle and heart glycogen deficiency. It has been described in three siblings (two brothers and their younger sister) 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.
2. The Symptoms:
Infants are asymptomatic at birth and in the neonatal period. Signs and symptoms typically begin in early childhood. Lack of early signs or symptoms does not exclude the diagnosis.
Normaly, the described patients showed no prior signs of distress before collapsing during a bout of exercise, resulting in death by cardiac arrest. Autopsy revealed hypertrophic cardiomyopathy. Muscle biopsy specimens obtained from the living patients showed lack of glycogen, predominance of oxidative fibers, and mitochondrial proliferation. Glucose tolerance was normal.
3. Actions to take in case of early diagnosis:
- Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in the gene GYS1) should continue breastfeeding, avoid fasting. Early treatment is essential in preventing chronic symptoms.
- GSD 0b is a lifelong disease that requires regular evaluation by a metabolic physician and metabolic nutritionist and a diet high in complex carbohydrates and protein to prevent hypoglycemia and ketosis, if present.
- Monitoring of cardiac and muscle fuction is essential. As there are just a few cases reported, the specific treatment is not very clear.
- Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
4. For more information
Biblio: Cameron, J. M., Levandovskiy, V., MacKay, N., Utgikar, R., Ackerley, C., Chiasson, D., Halliday, W., Raiman, J., Robinson, B. H. Identification of a novel mutation in GYS1 (muscle-specific glycogen synthase) resulting in sudden cardiac death, that is diagnosable from skin fibroblasts. Molec. Genet. Metab. 98: 378-382, 2009. PMID: PMID: 18358695.