SN5 SHORT NOTE 5M ★ High-yield

Classify the glycogen storage diseases. Describe Von Gierke and McArdle disease.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Glycogen storage diseases (glycogenoses) = inherited disorders of enzymes of glycogen synthesis or breakdown, causing abnormal quantity or structure of glycogen in tissues.

All are autosomal recessive except type VIII (X-linked)
The liver types cause hypoglycaemia and hepatomegaly; the muscle types cause exercise intolerance and cramps

The Important Types

Type	Name	Enzyme deficient	Chief features
I	Von Gierke	Glucose-6-phosphatase	Severe fasting hypoglycaemia, hepatomegaly, lactic acidosis, hyperuricaemia, hyperlipidaemia, doll-like face
II	Pompe	Lysosomal α-1,4-glucosidase (acid maltase)	Cardiomegaly and heart failure, hypotonia, death in infancy. The only lysosomal one
III	Cori / Forbes	Debranching enzyme	Milder Von Gierke; abnormal glycogen with short outer branches
IV	Andersen	Branching enzyme	Cirrhosis and liver failure; long unbranched chains
V	McArdle	Muscle phosphorylase	Exercise intolerance, cramps, myoglobinuria; NO rise in blood lactate on exercise; second-wind phenomenon
VI	Hers	Liver phosphorylase	Mild hepatomegaly, mild hypoglycaemia

WHY Type I Is So Severe

Glucose-6-phosphatase absent → Neither glycogenolysis nor gluconeogenesis can release free glucose → Severe fasting hypoglycaemia → G6P accumulates → diverted to glycolysis → lactic acidosis → and to the HMP shunt → ribose → hyperuricaemia → and to lipogenesis → hyperlipidaemia

It is the only enzyme common to the final step of both pathways — hence the severity

Diagnosis

Blood glucose, lactate, uric acid and lipids during fasting
Glucagon stimulation test — no rise in blood glucose in types I, III and VI
Ischaemic exercise test — no rise in venous lactate in McArdle disease; the classical bedside test
Enzyme assay on liver or muscle biopsy; genetic testing

Applied Aspects

Treatment of the liver forms — frequent small feeds, uncooked cornstarch overnight as a slow-release glucose source, avoiding fasting
McArdle disease — moderate exercise with the "second wind" as fatty acids take over; avoid intense exertion, which risks rhabdomyolysis and renal failure
Pompe disease is treated with enzyme replacement therapy (alglucosidase alfa) — one of the few glycogenoses with a specific treatment
These conditions illustrate that a single enzyme defect can be traced logically to every clinical feature

All questions in Carbohydrate Metabolism I: Glycolysis, TCA & Gluconeogenesis

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