Early diagnosis and improved treatment are leading to the potential for increased reproductive capability in
homocystinuria due to
cystathionine beta-synthase (CbetaS) deficiency, but information about reproductive outcome and risk of
thromboembolism in pregnancy is limited. To provide further information, clinical and biochemical information was obtained on women with maternal
homocystinuria, on their pregnancies and on the offspring. This information included blood sulphur
amino acids and total
homocysteine, CbetaS gene mutations and developmental and cognitive scores in the offspring. The study involved 15 pregnancies in 11 women, of whom 5 were
pyridoxine-nonresponsive and 6 were
pyridoxine-responsive. Complications of pregnancy included
pre-eclampsia at term in two pregnancies and superficial
venous thrombosis of the leg in a third pregnancy. One pregnancy was terminated and two pregnancies resulted in first-trimester
spontaneous abortions. The remaining 12 pregnancies produced live-born infants with normal or above-normal birth measurements. One offspring has multiple congenital anomalies that include
colobomas of the iris and choroid,
neural tube defect and
undescended testes. He is also mentally retarded and autistic. A second offspring has
Beckwith-Wiedemann syndrome. The remaining 10 offspring were normal at birth and have remained normal. There was no relationship between the severity of the biochemical abnormalities or the
therapies during pregnancy to either the
pregnancy complications or the offspring outcomes. The infrequent occurrences of
pregnancy complications, offspring abnormalities and maternal thromboembolic events in this series suggest that pregnancy and outcome in maternal
homocystinuria are usually normal. Nevertheless, a cautious approach would include careful monitoring of these pregnancies with attention to metabolic
therapy and possibly anticoagulation.