Testai FD, Gorelick PB. Hommocystinuria, organic acidurias and urea cycle disorder. Arch Neurol 2010; 67: 148-153.
Features of homocystinuria
Genetics (classical) Aut rec, chromosome 21, deficient cystathione synthase, 90 + mutations, elevated Homocystine and metabolite, methionine(or elevated homocysteine and normal methionine with MTHFR mutations or errors of B12 metabolism. Levels are over 100
. Stroke is due to atherosclerosis, dissection, or SVD
Clinical -- myopia, osteoporosis, mental retardation, decreased pigmentation of hair and skin, downwards ectopic lenses, dolichostenomelia, and if untreated, seizures, psychiatric disorders, thromboembolic events (PE, MI, stroke). Clinically there is an equal distribution of the milder B6 (pyridoxal phosphate) responsive form and more severe unresponsive form.
Thromboembolic events-- distribution-- 51 % peripheral vein (one fourth PE's), 32 % strokes, 11 % peripheral arterial, 4 % MI, 2 % other. 25 % stroke by age 15, half by age 30. Treatment of pyrodoxal phosphate responders delays first event.
Mechanism-- of thromboembolism is multi. Increased homocysteine causes premature atherosclerosis due to endovascular dysfunction due to deficient nitrous oxide and oxidative stress. Also, hypercoagulability due to increased thrombosis and platelet activation may affect stability of arterial wall and cause dissections, arterial thrombosis, and arteriopathy mimicking FMD.
Diagnosis-- Based on clinical and lab features. Brand reaction is screening test using urinary cyanide nitroprusside. Blood usually has elevated homocysteine and methionine and decreased cysteine. Urine excretion of homocysteine, homocystine (the oxidized form) and methionine occurs. Cystathionine B synthase cultures in fibroblasts, amniotic fluid and chorionic villi can be assessed.
Treatment-- judicious use of B6 (300-600 mg/day) to prevent PN. Folate, betaine and B12 cause conversion of homocysteine to methionine. A methionine free diet with cysteine supplementation is suggested. Vitamin C and antiplatelet agents are commonly used.
Features of homocystinuria
Genetics (classical) Aut rec, chromosome 21, deficient cystathione synthase, 90 + mutations, elevated Homocystine and metabolite, methionine(or elevated homocysteine and normal methionine with MTHFR mutations or errors of B12 metabolism. Levels are over 100
. Stroke is due to atherosclerosis, dissection, or SVD
Clinical -- myopia, osteoporosis, mental retardation, decreased pigmentation of hair and skin, downwards ectopic lenses, dolichostenomelia, and if untreated, seizures, psychiatric disorders, thromboembolic events (PE, MI, stroke). Clinically there is an equal distribution of the milder B6 (pyridoxal phosphate) responsive form and more severe unresponsive form.
Thromboembolic events-- distribution-- 51 % peripheral vein (one fourth PE's), 32 % strokes, 11 % peripheral arterial, 4 % MI, 2 % other. 25 % stroke by age 15, half by age 30. Treatment of pyrodoxal phosphate responders delays first event.
Mechanism-- of thromboembolism is multi. Increased homocysteine causes premature atherosclerosis due to endovascular dysfunction due to deficient nitrous oxide and oxidative stress. Also, hypercoagulability due to increased thrombosis and platelet activation may affect stability of arterial wall and cause dissections, arterial thrombosis, and arteriopathy mimicking FMD.
Diagnosis-- Based on clinical and lab features. Brand reaction is screening test using urinary cyanide nitroprusside. Blood usually has elevated homocysteine and methionine and decreased cysteine. Urine excretion of homocysteine, homocystine (the oxidized form) and methionine occurs. Cystathionine B synthase cultures in fibroblasts, amniotic fluid and chorionic villi can be assessed.
Treatment-- judicious use of B6 (300-600 mg/day) to prevent PN. Folate, betaine and B12 cause conversion of homocysteine to methionine. A methionine free diet with cysteine supplementation is suggested. Vitamin C and antiplatelet agents are commonly used.
