Lipoproteins transport cholesterol and triglycerides in the blood. Abnormal levels of these lipoproteins lead to lipoproteinaemia disorders. Glycogen abnormalities occur when cells store excess glycogen or fail to break it down properly. This may result from injury or inherited enzyme defects called Glycogen Storage Diseases (GSDs).
Abnormalities in Lipoproteinaemia
Lipoproteinaemia disorders may show either:
- High lipoproteins = Hyperlipoproteinaemia
- Low lipoproteins = Hypolipoproteinaemia
Hyperlipoproteinaemia
It is the most common abnormality and a major cause of atherosclerosis and coronary artery disease.
Types
1) Primary Hyperlipoproteinaemia: Caused by genetic defects in lipid metabolism.
2) Secondary Hyperlipoproteinaemia: Occurs due to other illnesses like diabetes, nephrotic syndrome or hypothyroidism.
WHO–Fredrickson Classification
- Type I: Lipoprotein lipase deficiency → ↑ chylomicrons → abdominal pain.
- Type IIa: Familial hypercholesterolemia → LDL receptor defect → ↑ LDL & cholesterol.
- Type IIb: apoB defect → ↑ LDL & VLDL.
- Type III: Familial dyslipoproteinemia → apoE defect → ↑ chylomicrons, IDL, triglycerides.
- Type IV: Mild hypertriglyceridemia → ↑ triglycerides; common CAD risk factor.
- Type V: Severe hypertriglyceridemia → ↑ VLDL & TG; premature vascular disease.
Hypolipoproteinaemia
Less common; includes:
- Abetalipoproteinemia: Reduced apoB → ↓ chylomicrons, VLDL, LDL → poor fat absorption, neurological issues due to low myelin.
- Tangier disease (Familial α-lipoprotein deficiency): ABC transporter defect → very low HDL → early coronary artery disease.
Glycogen Infiltration
In cell injury, the cell loses normal metabolic activity, resulting in accumulation of substances like glycogen.
Features
- Glycogen accumulates in vacuoles.
- Detected using special stains like PAS (Periodic Acid-Schiff).
- Common in uncontrolled diabetes due to high glucose → excess glycogen storage.
- Also seen in chronic kidney disease due to reduced kidney function.
Glycogen Storage Diseases (GSDs)
GSDs are inherited disorders where glycogen synthesis or breakdown is defective. They affect liver, muscle or multiple organs.
Main Groups of GSDs
- Liver GSDs
- Muscle GSDs
- Generalized GSDs
Liver Glycogenoses Include:
GSD I, III, IV, VI, IX, and GSD 0.
Major Glycogen Storage Diseases
1. GSD I — Von Gierke Disease
Cause: Glucose-6-phosphatase (G6Pase) deficiency → liver cannot release glucose → glycogen accumulates.
Symptoms:
- Enlarged liver
- Low blood sugar (especially fasting)
- High lactate, fats and uric acid
- Delayed growth and puberty
Treatment:
- Glucose via nasogastric tube initially
- Cornstarch orally in older children for slow glucose release
2. GSD III — Cori Disease
Cause: Debrancher enzyme deficiency → incomplete glycogen breakdown → abnormal glycogen in liver, muscle and heart.
Symptoms:
- Swollen abdomen
- Low blood glucose
- Growth delay
- Muscle weakness
Diagnosis:
Liver biopsy shows swollen cells with abnormal glycogen.
Treatment:
Protein supplements to support muscle function.
3. GSD IV — Andersen Disease
Cause: Branching enzyme deficiency → abnormal long-chain glycogen stored in liver and muscle.
Symptoms:
- Growth delay
- Enlarged liver
- Progressive liver cirrhosis → liver failure
Treatment:
Liver transplantation only effective option. Most children die before age 2.
4. GSD VI — Hers Disease
Cause: Liver phosphorylase deficiency → inability to break down glycogen.
Symptoms:
- Hepatomegaly
- Hypoglycemia
- Growth retardation
- High lipids
Diagnosis:
Blood sugar and cholesterol tests; liver function tests.
Treatment:
Frequent feeding to prevent low blood sugar.
5. GSD IX — Phosphorylase Kinase Deficiency
Cause: PhK deficiency → glycogen accumulates in liver, muscle, RBCs and sometimes heart.
Symptoms:
- Enlarged liver
- Low blood sugar
Diagnosis:
Blood profiling, liver biopsy.
Treatment:
High-carbohydrate diet, adequate protein and avoiding long fasting.
6. GSD 0 — Glycogen Synthase Deficiency
Cause: Defective glycogen synthase → reduced liver glycogen.
Symptoms:
- Drowsiness before breakfast
- Fatigue, paleness, vomiting
- Muscle weakness and cramps
Diagnosis:
Blood glucose tests, liver function monitoring.
Detailed Notes:
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