IllnessGlycogen storage disorders, differential diagnosis

NGS +

[[Sanger]]

Glycogen storage diseases (glycogenoses, GSDs) are metabolic disorders caused by enzyme defects due to disturbed glycogen synthesis, glycogen degradation or glycolysis, typically in the muscles. Depending on the enzyme defect and its expression in the liver, kidney, skeletal muscle and/or heart, the clinical signs vary from one disease to another. Liver GSDs frequently occur with hypoglycemia, ketotic hypoglycemia after fasting, hyperketonaemia, hypoglycemia, postprandial hyperglycemia, postprandial hyperlactataemia and with hepatomegaly. Muscle GSDs occur in two ways: with exercise intolerance and rhabdomyolysis or fixed muscle weakness without rhabdomyolysis. Stress intolerance and rhabdomyolysis frequently occur in dynamic disorders such as McArdle and Tarui disease, while fixed muscle weakness without rhabdomyolysis occurs in cytoplasmic disorders associated with glycogenolysis defects. Depending on the GSD, the first symptoms can be observed early in infancy and into middle age. Most GSDs are inherited autosomal recessively, rarely autosomal dominantly or X-linked. The DNA diagnostic yield is not known exactly. Therefore, an inconspicuous genetic finding does not exclude a suspected clinical diagnosis.

Reference: file:///C:/Users/EppleJoe/AppData/Local/Temp/atm-06-24-474.pdf

https://www.nature.com/articles/gim2015217.pdf?origin=ppub

• DD: Von Gierke, Pompe, Anderson, McArdle, Tarui, Danon, Hers, Fanconi-Bickel et al.
• Allelic: Cardiomyopathy, hypertrophic 6 (PRKAG2)
• Allelic: Cirrhosis due to liver phosphorylase kinase deficiency (PHKG2)
• Allelic: Diabetes mellitus, noninsulin-dependent (SLC2A2)
• Allelic: Polyglucosan body disease, adult form (GBE1)
• Allelic: Polyglucosan body myopathy 2 (GYG1)
• Allelic: Wolff-Parkinson-White syndrome (PRKAG2)
• Congenital disorder of glycosylation, type It (PGM1)
• Danon disease (LAMP2)
• Epilepsy, progressive myoclonic 2A, Lafora (EPM2A)
• Epilepsy, progressive myoclonic 2B, Lafora (NHLRC1)
• Fanconi-Bickel syndrome (SLC2A2)
• Fructose intolerance, hereditary (ALDOB)
• Fructose-1,6-bisphosphatase deficiency (FBP1)
• Glycogen content in skeletal muscle, increased (PRKAG3)
• Glycogen storage disease 0, liver (GYS2)
• Glycogen storage disease 0, muscle (GYS1)
• Glycogen storage disease II (GAA)
• Glycogen storage disease IIIa, IIIb (AGL)
• Glycogen storage disease IV (GBE1)
• Glycogen storage disease IXc (PHKG2)
• Glycogen storage disease Ia (G6PC)
• Glycogen storage disease Ib, Ic (SLC37A4)
• Glycogen storage disease VI (PYGL)
• Glycogen storage disease VII (PFKM)
• Glycogen storage disease X (PGAM2)
• Glycogen storage disease XI (LDHA)
• Glycogen storage disease XII (ALDOA)
• Glycogen storage disease XIII (ENO3)
• Glycogen storage disease XV (GYG1)
• Glycogen storage disease of heart, lethal congenital (PRKAG2)
• Glycogen storage disease, type IXa1, type IXa2 (PHKA2)
• Lactate dehydrogenase-B deficiency (LDHB)
• McArdle disease, Glycogen storage disease V (PYGM)
• Muscle glycogenosis (PHKA1)
• Phosphoglycerate kinase 1 deficiency (PFK1)
• Phosphorylase kinase deficiency of liver and muscle, AR (PHKB)
• Polyglucosan body myopathy 1 +/- immunodeficiency (RBCK1)