Elevated levels of homocysteine—a condition known as hyperhomocysteinemia—are associated with several serious diseases, especially those affecting the cardiovascular, nervous, and skeletal systems. While homocysteine is a normal metabolic intermediate, its accumulation becomes toxic when not properly regulated.
⚠️ Diseases and Disorders Associated with Homocysteine
❤️ 1. Cardiovascular Disease (CVD)
- Strongly linked to elevated homocysteine levels.
- Homocysteine damages the endothelium, promotes inflammation, and increases oxidative stress.
🩺 Associated conditions:
- Atherosclerosis
- Coronary artery disease
- Myocardial infarction (heart attack)
- Thrombosis (blood clots)
High homocysteine = ↑ risk of heart and vessel damage.
🧠 2. Stroke
- Homocysteine promotes blood clot formation, which can obstruct brain arteries.
- Also contributes to small vessel disease and cerebral microangiopathy.
🧬 3. Homocystinuria
- A rare inherited disorder (usually due to CBS enzyme deficiency) causing extremely high homocysteine levels.
👶 Seen in children with:
- Developmental delays
- Lens dislocation
- Skeletal abnormalities
- Vascular complications
Requires lifelong management with B6, B12, folate, and betaine.
🧠 4. Neurodegenerative and Cognitive Disorders
Alzheimer’s disease & dementia:
- Elevated homocysteine is a risk factor for cognitive decline.
- May increase amyloid plaque formation and brain atrophy.
Parkinson’s disease:
- Homocysteine may contribute to neurotoxicity and dopaminergic neuron damage.
🤰 5. Pregnancy Complications
- High homocysteine levels are linked to:
- Neural tube defects (e.g., spina bifida)
- Pre-eclampsia
- Placental abruption
- Miscarriage
Folate deficiency is often a contributing factor.
🦴 6. Osteoporosis
- Homocysteine may interfere with collagen cross-linking in bone matrix.
- High levels have been associated with:
- Reduced bone mineral density
- Increased fracture risk
🧪 Common Causes of Elevated Homocysteine
| Cause | Mechanism |
| Vitamin B12 deficiency | Impaired remethylation to methionine |
| Folate deficiency | ↓ 5-methyltetrahydrofolate for remethylation |
| Vitamin B6 deficiency | Blocks transsulfuration to cysteine |
| Kidney disease | Reduced excretion |
| Genetic mutations | e.g., MTHFR, CBS enzyme mutations |
| Hypothyroidism | Slowed metabolism of homocysteine |
📊 Summary Table
| Disease/Condition | Relation to Homocysteine |
| Cardiovascular disease | ↑ Homocysteine damages vessels |
| Stroke | ↑ Promotes thrombosis |
| Homocystinuria | Genetic accumulation of homocysteine |
| Alzheimer’s disease | Neurotoxic effects |
| Neural tube defects | Folate-related methylation failure |
| Osteoporosis | Interferes with bone collagen |