All classic disorders of carbohydrate metabolism result from a specific enzyme defect. Almost all of these enzyme defects are inherited in an autosomal recessive fashion. These metabolic diseases may be classified into three main groups, affecting the metabolism of glycogen, galactose, and fructose. Clinical manifestations are variable and range from occasional innocuous hypoglycemia to severe cognitive impairment and death within a few weeks of birth. Newborn screening enables the early detection of metabolic diseases and early initiation of appropriate dietary restrictions helps prevent disease manifestations.
- Glycogen storage disorders (GSDs; glycogenoses) are hereditary metabolic disorders characterized by defects in the enzymes responsible for glycogenolysis or glycolysis.
- 13 different types have been described
- All types cause abnormal accumulation of glycogen due to impaired glycogen metabolism.
- Only a few GSDs are relevant in clinical practice (see “Types of GSD” below).
- Incidence: up to 1:20,000 live births 
- Age of onset: presentation during infancy or childhood
- Sex: ♂ = ♀
- Mode of inheritance: mostly autosomal recessive (types I, II, III, and V)
- Defective enzymes responsible for glycolysis or glycogenolysis → impaired glycogen metabolization → ↑ storage of either normal or abnormal glycogen
- Liver, heart, and muscle are the most common sites of glycogen storage and are, therefore, predominantly affected.
Types of GSD
|Overview of types of GSD |
|Relative frequency||Gene defect and deficient enzyme||Role of the enzyme||Characteristic features|
|Type I (von Gierke disease)||Type 1a|| |
|Type II (Pompe disease)|| |
|Type III (Cori disease)|| || |
|Type IV (Andersen disease)|| || |
|Type V (McArdle disease)|| || |
|Type VI (Hers disease)|| |
The first six glycogen storage diseases can be remembered with the mnemonic “a Very Presumptuous Corgi Ambles in the Middle of the Highway.”
McArdle affects the Muscles.
- Seen in types II, III, IV, V
- Two groups of skeletal muscle symptoms are seen:
- Defects of muscle glycogenolysis and muscle glycolysis:
- Defects of muscle glycogenesis (type IV) and lysosomal glycogenolysis (type II): progressive weakness of extremities and trunk (proximal myopathy)
- Seen in several types (e.g., type II, type III)
- Hypertrophic cardiomyopathy and/or conduction defects are most common in type II.
- Liver involvement
Additional clinical manifestations
- Growth delay/growth retardation/failure to thrive: types I, II, III, IV
- Anemia: type I
- Hyperlipidemia: types I, III
- Macroglossia: type II
- Lactic acidosis: type I
- Hyperuricemia: type I
“Pompe punishes pump, liver, and muscle.”
- Initial tests
- Confirmatory test: DNA testing for the gene defects
- Muscle GSD 
Ischemic forearm test: an important test to evaluate if a patient has a metabolic disorder of muscle function
- A sphygmomanometer cuff is tied around the arm and inflated to beyond systolic blood pressure. The patient is then asked to repeatedly form a fist. The cuff is then deflated and multiple blood samples are taken to measure serum lactate levels.
- The normal response to an ischemic exercise test is an increase in the levels of lactate as a result of anaerobic metabolism of glucose.
- In the case of GSD type III and type V,, not enough glucose is produced from glycogen. As a result, lactate levels do not rise.
- ↑ Creatine kinase
- Electroneuromyography: to identify proximal myopathy
- EKG and/or echocardiography: to identify cardiac hypertrophy and conduction blocks
- Ischemic forearm test: an important test to evaluate if a patient has a metabolic disorder of muscle function
- Liver GSD
- Muscle GSD 
- Enzyme replacement therapy is available for some forms of GSD
- A liver transplant may be required in the case of liver GSD that progress to liver cirrhosis and/or result in poor metabolic control.
- Cardiac involvement
|Overview of types of galactosemia |
|Galactokinase deficiency||Classic galactosemia||Uridine diphosphate galactose-4-epimerase deficiency|
|Mode of inheritance|
|Enzyme|| || |
|Relative frequency|| || || |
|Role of enzyme|| || || |
|Disease severity|| || |
|Effect of enzyme deficiency|| |
Disorders of fructose metabolism
|Overview of disorders of fructose metabolism |
|Hereditary fructose intolerance||Essential fructosuria|
|Incidence|| || |
|Gene defect|| || |
|Mode of inheritance|
|Role of enzyme|| |
|Effect of enzyme deficiency|
|Age of onset|| || |
|Treatment|| || |