Homocysteinemia

Sample

1. This test can be done on the serum of the patient.
2. Separate serum immediately and freeze within one hour.
3. This can be detected in the urine.

Precautions

1. 10 to 12 hours of fasting before the test is required.
2. Patients with renal diseases will have an increased level of homocysteine. This is due to the poor excretion of the protein.
3. The patient with a low intake of Vit. B has increased the level of homocysteine.
4. Men have a higher level than women.
5. Smoking will lead to a higher level of homocysteine.
6. Drugs increase Homocysteine levels like methotrexate, nitrous oxide, phenytoin, and carbamazepine.
7. Oral contraceptives influence the level.

Why homocysteine is measured (Indications):

1. To diagnose homocystinuria.
   1. This is done to measure the plasma level of homocysteine (homocysteinemia).
   2. It is done to find genetic or acquired homocysteine excess.
2. The patients are at risk of developing folate deficiency and cobalamin.
3. In patients with unexplained anemia.
4. Recurrent spontaneous abortion.
5. Delayed development or failure to survive in infants.
6. In cases of peripheral neuropathy and myelopathy.
7. For the evaluation of cardiovascular disease.
8. In which patients homocysteine to be estimated:
   1. This can be used for the surveillance of malnutrition.
   2. In vegetarians who are not taking a supplement of B12.
   3. In old patients above the age of 75 years.
   4. The patient is on the treatment of antiepileptic drugs and methotrexate.
   5. Increased risk for pregnancy complications and neural tube defect.
9. Homocysteine in a patient with coronary disease:
   1. Patients <40 years of age with a history of cardiovascular disease exclude homocysteinemia.
   2. Patients at high risk for cardiovascular disease should be tested every 3 to 5 years.
10. How often homocysteine should be tested:
    1. This may be measured every 3 to 5 years.
    2. In newborns at the age of 3 to 5 days.

Pathophysiology of Homocysteinemia

1. Homocysteine is a sulfur-containing amino acid.
   1. It is formed during the metabolism of methionine.
   2. It requires folic acid as a cofactor.
   3. It may be catabolized to cysteine in the presence of Vitamin B as a cofactor.

2. Homocysteinemia is the elevation of homocysteine in the blood.
3. Vitamins are the cofactor involved in the metabolism of Methionine to homocysteine.
   1.  Folic acid acts as a cofactor.
   2. The common non-genetic elevated level of homocysteine caused is a deficiency of B6, B12, or folate.
   3. Homocysteine does not accumulate in the blood because it is unstable in an aqueous solution; when it is present in excess, it will undergo oxidation and give rise to homocystine.

Homocysteinemia may be due to:

1. Genetic predisposition.
2. Nutritional and environmental factors.
3. Specific medications.
4. Amino acids are naturally made products, which are the building blocks of all the proteins in the body.
5. Homocysteine is an intermediate amino acid formed during the metabolism of methionine.
6. So homocysteine blood level is helpful in the diagnosis of deficiency of these vitamins.
7. Homocysteine levels may be increased in megaloblastic anemia patients before other abnormal tests are found.
8. Homocysteine may be used as an early indicator of these patients, and treatment can be started early.

Homocysteine also appears to cause:

1. Increased atherosclerosis by causing damage to the endothelial lining.
   1. Increased LDL deposition.
   2. Increase vascular smooth muscle growth.
2. Increased risk for vascular diseases.
3. Increased risk of venous thrombosis.
4. Increased risk for pregnancy complications and neural tube defects.
5. The patient with increased homocysteine has 5 times more risk of stroke, dementia, and Alzheimer’s disease.
   1. Increased homocysteine level is also a risk factor for osteoporotic fractures in older men and women.
   2. Raising the homocysteine level will increase the risk of coronary artery disease and thrombosis.
6. Homocysteinemia >15 µmol/L leads to:
   1. Increased atherosclerosis.
      1. Although lipoproteins are normal.
      2. In the absence of other risk factors.
7. Some researcher believes that these patients may be treated by giving vitamins B6, B12, and folate.
8. Affected children suffer from homocystinuria and had very premature increased atherosclerosis at an early age.

Clinical Presentations of Homocystenemia

1. Increased Homocysteine is associated with:
   1. Various vascular and cardiovascular diseases.
   2. The birth defects.
   3. Complications in the pregnancy.
   4. Psychiatric disorders.
   5. Mental impairment in older adults.

Normal

Homocysteine

Source 2

• Fasting level = 4 to 14 µmol/L  (0.54 to 2.3 mg/L).

Source 4

•  4 to 17 µmol/L

Another source

•  Serum = 13 to 18  µmol/L
• Plasma = 10 to 15 = µmol/L
• Children = 3.7 to 10.3 µmol/L

Urine 

• Negative

Interpretations

• Normal less than 15 µmol/L
  1. Moderate increase = 5 to 30 µmol/L.
  2. Intermediate increase = 30 to 100 µmol/L.
  3. Severe disease = >100 µmol/L.

Increased Homocysteine is seen in:

1. Folic acid deficiency.
2. Vit.B12 deficiency.
3. Cardiovascular diseases.
4. Cerebrovascular diseases.
5. Peripheral vascular diseases.
6. Malnutrition.
7. Homocystinuria.

Recommendations for the raised total homocysteine:

1. Total homocysteine is recommended in patients with cardiovascular disease <40 years of age to exclude the homocystinuria.
2. Total homocysteine is measured in patients with cardiovascular disease to know the prognosis and mortality.
3. Cardiovascular disease patients with >15 µmol/L are high-risk groups. These patients need all kinds of precautions to prevent cardiovascular attacks. Such patients need a healthy life.

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