Glycogen Storage Diseases
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Direct answer
Glycogen storage diseases are inherited defects in the synthesis or breakdown of glycogen, and each type is defined by its enzyme. Von Gierke disease, type I, is the classic hepatic form and results from glucose-6-phosphatase deficiency. Hepatomegaly, fasting hypoglycaemia and lactic acidosis are the usual findings in the liver-predominant types, while the heart and muscle are the main targets in others.
What you must remember
- Von Gierke disease (type I): glucose-6-phosphatase deficiency, with a doll-like face, hepatomegaly, fasting hypoglycaemia, lactic acidosis, hyperlipidaemia and hyperuricaemia.
- Type Ib: a glucose-6-phosphate transporter defect that adds neutropenia and recurrent bacterial infections to the type I picture.
- Pompe disease (type II): acid alpha-glucosidase deficiency, the only glycogen storage disease that is also lysosomal, with cardiomyopathy, hypotonia and macroglossia.
- Cori disease (type III): debranching enzyme deficiency, with hepatomegaly and hypoglycaemia that often improve with age, and myopathy in some.
- Andersen disease (type IV): branching enzyme deficiency that produces abnormal polyglucosan and progressive cirrhosis.
- McArdle disease (type V): muscle phosphorylase deficiency, with exercise cramps and myoglobinuria but no lactate rise after ischaemic exercise.
- Hers disease (type VI): liver phosphorylase deficiency, usually milder, with hepatomegaly and a good prognosis.
- Feeding in type I: frequent feeds, nocturnal feeding and uncooked cornstarch, with fructose, galactose and sucrose avoided.
Matching the enzyme defect to the organ involved
The organ involved narrows the type faster than the enzyme name does, and examiners reward that reasoning in every paediatrics paper. Liver-predominant types usually present with childhood hypoglycaemia, while muscle types typically present with exercise intolerance.
| Type | Enzyme defect | Main organ | Key feature |
|---|---|---|---|
| I (von Gierke) | Glucose-6-phosphatase | Liver, kidney | Fasting hypoglycaemia, lactic acidosis |
| II (Pompe) | Acid alpha-glucosidase | Heart, muscle | Cardiomyopathy, hypotonia |
| III (Cori) | Debranching enzyme | Liver, muscle | Hypoglycaemia that eases with age |
| IV (Andersen) | Branching enzyme | Liver | Progressive cirrhosis |
| V (McArdle) | Muscle phosphorylase | Muscle | Exercise cramps, myoglobinuria |
The liver is affected in types I, III, IV and VI, which is why hepatomegaly dominates examination questions on this topic. Heart involvement typically marks Pompe disease, so an echocardiogram belongs to the initial assessment of any infant with hypotonia and cardiomegaly. Ask about the organ involved before naming the enzyme in a viva or MCQ, since the clinical story points there first.
Where the exam tests glycogen storage diseases
Examiners test the enzyme-organ match, the lactate pattern and the feeding strategy. These traps are common.
- Trap: treating fasting hypoglycaemia in type I with a single glucose bolus. Correct: frequent feeds, nocturnal feeds or uncooked cornstarch maintain glucose overnight, because the liver cannot release glucose.
- Trap: expecting lactate to rise after exercise in McArdle disease. Correct: lactate fails to rise during ischaemic forearm exercise, since muscle glycogen cannot be broken down to glucose.
- Trap: calling Pompe disease a simple liver glycogen disorder. Correct: Pompe is lysosomal, causes cardiomyopathy and hypotonia, and has enzyme replacement available.
Frequently asked questions
Which glycogen storage disease is also a lysosomal disorder?
Pompe disease, type II, is the only glycogen storage disease that is also a lysosomal storage disorder. It is caused by acid alpha-glucosidase deficiency, which breaks down glycogen inside lysosomes.
How is hypoglycaemia prevented in glycogen storage disease type I?
Hypoglycaemia in glycogen storage disease type I is prevented with frequent feeds, nocturnal feeding and uncooked cornstarch. Fructose, galactose and sucrose are avoided because they add to lactic acidosis and raise triglyceride levels.
Why does McArdle disease cause cramps without a lactate rise?
McArdle disease is muscle phosphorylase deficiency, so muscle glycogen cannot be broken down to glucose-1-phosphate. Lactate therefore fails to rise during ischaemic forearm exercise, which is the diagnostic test, while cramps and myoglobinuria follow strenuous effort.
Which glycogen storage disease causes progressive cirrhosis?
Andersen disease, glycogen storage disease type IV, causes progressive cirrhosis because branching enzyme deficiency produces abnormal polyglucosan. It typically presents in infancy with hepatomegaly and poor growth.