Introduction:
Metabolic disorders of carbohydrate metabolism are a group of hereditary conditions caused by defects in enzymes responsible for carbohydrate breakdown or utilization. These disorders prevent the normal processing of sugars, leading to their accumulation and resulting in metabolic disturbances.
Most of these conditions are inherited genetic disorders caused by defective genes passed from parents to children. In many cases, both parents are carriers of the abnormal gene but do not show symptoms themselves. Some disorders are X-linked, meaning a single defective gene can cause the disease in males.
Overview of Carbohydrate Metabolism
Carbohydrates are composed of simple and complex sugars. Before absorption and utilization, they must be broken down into simple monosaccharides such as glucose, fructose, and galactose. For example:
- Sucrose (table sugar) → glucose + fructose
- Lactose (milk sugar) → glucose + galactose
These reactions require specific enzymes. If an enzyme is missing or defective, the associated sugar or intermediate accumulates, leading to toxic effects and metabolic complications.
Common Disorders of Carbohydrate Metabolism
- Galactosemia
- Glycogen Storage Diseases (GSDs)
- Hereditary Fructose Intolerance
- Pyruvate Metabolism Disorders
- Diabetes Mellitus
Let’s discuss two major conditions: Diabetes Mellitus and Glycogen Storage Diseases.
1. Diabetes Mellitus
Diabetes Mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels (hyperglycemia) due to defective insulin secretion, insulin action, or both.
Types:
- Type 1 Diabetes Mellitus: Autoimmune destruction of pancreatic β-cells leading to absolute insulin deficiency. Commonly seen in childhood or adolescence.
- Type 2 Diabetes Mellitus: Caused by insulin resistance and relative insulin deficiency. Common in adults and associated with obesity and sedentary lifestyle.
Biochemical Changes:
- Decreased glucose uptake by tissues (especially muscle and adipose tissue)
- Increased gluconeogenesis and glycogenolysis in the liver
- Enhanced lipolysis leading to elevated free fatty acids
- Ketone body formation causing diabetic ketoacidosis in severe cases
Clinical Features:
- Polyuria (frequent urination)
- Polydipsia (excessive thirst)
- Polyphagia (increased hunger)
- Weight loss and fatigue
- In severe cases: ketoacidosis, dehydration, and coma
Complications:
- Diabetic nephropathy (kidney damage)
- Retinopathy (eye damage)
- Neuropathy (nerve damage)
- Cardiovascular disease
Management:
- Dietary control and regular exercise
- Insulin therapy for Type 1 diabetes
- Oral hypoglycemic drugs for Type 2 diabetes
- Monitoring blood glucose and HbA1c levels
2. Glycogen Storage Diseases (GSDs)
Glycogen Storage Diseases are a group of inherited disorders caused by enzyme deficiencies in glycogen metabolism. The result is abnormal accumulation of glycogen or its intermediates in tissues, particularly the liver and muscles.
Depending on which enzyme is deficient, the severity and affected organs vary. Some forms are mild and manageable, while others are severe or even fatal.
A) Von Gierke’s Disease (Type I GSD)
Deficiency: Glucose-6-phosphatase (in liver, kidney, and intestine)
Features:
- Severe hypoglycemia
- Accumulation of glycogen in liver and kidney → hepatomegaly
- Associated metabolic disturbances: hyperuricemia, hyperlipemia, and ketosis
Incidence: 1 in 200,000 births
B) Pompe’s Disease (Type II GSD)
Deficiency: Lysosomal α-glucosidase
Pathology: Lysosomes cannot degrade glycogen, leading to its accumulation in all tissues, especially the heart.
Symptoms: Cardiomegaly, muscle weakness, and respiratory failure.
Outcome: Fatal within the first 2 years of life due to cardiorespiratory failure.
C) Cori’s Disease (Type III GSD)
Deficiency: Debranching enzyme
Consequence: Accumulation of limit dextrin (a partially degraded glycogen molecule) in the liver.
Alternate Name: Limit Dextrinosis
D) Anderson’s Disease (Type IV GSD)
Deficiency: Branching enzyme
Effect: Accumulation of amylopectin-like material in liver, spleen, and heart.
Outcome: Fatal, often in early childhood due to liver cirrhosis and heart failure.
E) McArdle’s Syndrome (Type V GSD)
Deficiency: Muscle phosphorylase
Effect: Glycogen accumulates in muscles; lactic acid levels fail to rise after exercise.
Symptoms: Painful muscle cramps and reduced exercise tolerance.
F) Her’s Disease (Type VI GSD)
Deficiency: Liver phosphorylase
Effect: Defective glycogenolysis leading to glycogen accumulation in the liver.
Summary Table: Glycogen Storage Diseases
| Type | Deficient Enzyme | Main Organ Affected | Key Features |
|---|---|---|---|
| I (Von Gierke) | Glucose-6-phosphatase | Liver, Kidney | Hypoglycemia, Hepatomegaly, Hyperuricemia |
| II (Pompe) | Lysosomal α-glucosidase | Heart, Muscle | Cardiomegaly, Fatal by age 2 |
| III (Cori) | Debranching enzyme | Liver | Limit dextrin accumulation |
| IV (Anderson) | Branching enzyme | Liver, Heart | Amylopectin accumulation, Fatal |
| V (McArdle) | Muscle phosphorylase | Muscle | Exercise cramps, No lactic acid increase |
| VI (Her’s) | Liver phosphorylase | Liver | Glycogen accumulation, Mild hypoglycemia |
Detailed Notes:
For PDF style full-color notes, open the complete study material below: