How can I differentiate between various types of glycogen storage disorders based on clinical presentation and biochemical findings?

Glycogen storage disorders (GSDs) can be differentiated based on their clinical presentation and biochemical findings by focusing on key organ involvement, symptom onset, and specific enzyme deficiencies.

For example, GSD type I (von Gierke disease) typically presents in infancy with severe fasting hypoglycaemia, lactic acidosis, hyperuricaemia, and hyperlipidaemia due to glucose-6-phosphatase deficiency affecting gluconeogenesis and glycogenolysis in the liver and kidney ¹.

GSD type III (Cori or Forbes disease) is characterised by hepatomegaly, hypoglycaemia, and progressive myopathy or cardiomyopathy due to debranching enzyme deficiency, with clinical neuromuscular and cardiac involvement becoming more prominent with age (Berling É et al., 2021).

GSD type VI (Hers disease) presents with mild to moderate hepatomegaly and mild hypoglycaemia, often with normal growth and no significant muscle involvement, caused by liver phosphorylase deficiency (Grünert et al., 2021). Biochemically, it shows elevated liver transaminases and mild ketotic hypoglycaemia.

Other types, such as GSD type II (Pompe disease), primarily affect muscle with progressive myopathy and cardiomyopathy due to acid alpha-glucosidase deficiency, and can be differentiated by enzyme assay and genetic testing ¹.

Biochemical differentiation relies on specific enzyme assays from liver or muscle biopsy and genetic testing, alongside characteristic laboratory findings such as hypoglycaemia patterns, lactate levels, lipid profiles, and presence or absence of ketones during hypoglycaemia ¹.

In summary, clinical differentiation hinges on the pattern of organ involvement (liver, muscle, heart), age of onset, and symptom severity, while biochemical differentiation depends on enzyme activity assays and metabolic profiles.