Homocystinuria

= HOMOCYSTINURIA =

These are a series of inborn errors of metabolism that are characterized by

increased homocysteine levels in blood and urine.

These are autosomal recessive disorders and are seen in 1 in 200,000 births.

Normal homocysteine level in blood is 5–15 micromol/L. It can rise to 50-100

times the normal level in diseases. Moderate increase is seen in aged people,

vitamin B12 or B6 deficiency, smokers and alcoholics and also in

hypothyroidism.

Elevated homocysteine levels in blood is associated with increased risk of

coronary artery disease through increased oxidant stress, impaired endothelial

function, and induction of thrombosis.

= Causes of homocystinuria =

1. Cystathionine beta synthase deficiency (defective CBS gene)

2. Deficient N 5 ,N 10 -Methyl THFA reductase (defective MTHFR gene)

3. Cobalamin (B12) deficiency.

= Clinical manifestations =

1. Mental Retardation and Charlie Chaplin gait (Bilateral extorsion of the

tibia).

2. Involvement in the eye: Ectopia Lentis (Subluxation of lens) and severe

Myopia are seen.

3. Increased platelet adhesiveness and increased risk of intravascular

thrombosis due to activation of Hagemann’s factor (clotting factor XII).

= Diagnosis =

Cyanide-Nitroprusside test is positive in urine. Urinary homocysteine exceeds

300 mg/24 hours.

Treatment:

Diet low in methionine and vitamin B6 therapy along with folate and B12

supplements. Betaine therapy is usually added to the therapeutic regimen.