Homocystinuria

Homocystinuria

It is an inborn error of Methionine metabolism in which there is deficiency of enzyme cystathionine b-synthase

Homocysteine is converted to methionine. In homocystinuria there is impaired conversion of homocysteine to methionine, The sulfur atom of the essential amino acid methionine is transferred ultimately to cysteine by the transsulfuration pathway. In one of these steps, homocysteine condenses with serine to form cystathionine. This reaction is catalyzed by the pyridoxal phosphate-dependent enzyme cystathionine b-synthase.

Homocysteine and methionine accumulate in cells and body fluids; cysteine synthesis is impaired, resulting in reduced concentrations of this amino acid and its disulfide form cystine.

Homocystinuria is relatively common in Ireland (1 in 60,000 births) but rare elsewhere (less than 1 in 200,000 births).

This genetic defect is also seen in consanguineous marriages.

Features:
Mental retardation
Venous thromboses- a major cause of morbidity
Osteoporosis
Hair often fine & brittle. Malar flush. Ectopia lentis, myopia.
Convulsions in about 10%. Psychiatric disturbances.
Skeletal features resembling Marfan syndrome – in 50 % of cases.

Diagnosis:
Detection of Homocysteine in urine.

Range of Homocysteine.in blood

  • Normal ( Male) : – 8.0 – 14.0 mmol/L
  • Normal (Female) : – 6.0 -12.0 mmol/L
  • Moderate homocystenaemia : – 16-30 mmol/L
  • Intermediate homocystenaemia : – 31-100 mmol/L
  • Severe homocystenaemia : – > 100 mmol/L

Treatment:
Pyridoxine 20-300 mg per day.

Restricted intake of methionine plus cystine supplements.
Administration of choline or betaine to enhance remethylation of homocystine

Homocysteine is an amino acid that’s normally produced in the body in small amounts from the amino acid methionine. Homocysteine’s role in the body is to control growth, and support bone and tissue formation.
Scientists have known that people with high concentrations of the amino acid homocysteine in the blood are at a much higher risk for stroke and heart disease. When homocysteine levels rise, they begin to damage arteries and stimulate growth of arteriosclerotic plaques which leads to heart disease.

High levels of homocysteine can be caused by

  • Vitamin deficiencies
  • Normal aging
  • Thyroid problems
  • Kidney disease
  • Genetic disorders like Homocystinuria.

Study shows folic acid and vitamins B6 and B12 can decrease homocysteine concentrations in the blood – reducing the risk of heart disease.

Anyone who has a high risk for heart disease either from family history or poor nutritional background, or who has early signs of heart disease probably should take vitamin supplements to control their homocysteine level and stop the arteriosclerotic process.

Severe deficiency of Folic Acid, vitamin B6 and B12 in the elderly may result in elevated serum homocysteine levels. Its a new risk factor for the Cardiac disease. Deficiency of each one of these vitamins may lead to accumulation of homocysteine which is known to have toxic effect on the vascular tissue.

A study found high levels of homocysteine in second generation Indian immigrants as compared to Europeans.

Folic acid rich foods are – Pulses, dried beans, green leafy vegetables.

Pyridoxine ~ Vitamin B6