Reproductive fitness in maternal homocystinuria due to cystathionine β‐synthase deficiency

• Published in: Journal of inherited metabolic disease Vol. 25; no. 4; pp. 299 - 314
• Main Authors: Levy, H. L., Vargas, J. E., Waisbren, S. E., Kurczynski, T. W., Roeder, E. R., Schwartz, R. S., Rosengren, S., Prasad, C., Greenberg, C. R., Gilfix, B. M., MacGregor, D., Shih, V. E., Bao, L., Kraus, J. P.
• Format: Journal Article
• Language: English
• Published: Dordrecht Kluwer Academic Publishers 01.08.2002; Springer
• Subjects: Adolescent; Adult; Amino Acids - blood; Amino Acids, Sulfur - metabolism; Aminoacid disorders; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Child; Child, Preschool; Cystathionine beta-Synthase - deficiency; Cystathionine beta-Synthase - genetics; Delivery, Obstetric; DNA Mutational Analysis; Drug Resistance; Errors of metabolism; Female; Homocystine - blood; Homocystinuria - complications; Homocystinuria - etiology; Homocystinuria - genetics; Humans; Infant, Newborn; Medical sciences; Metabolic diseases; Nutritional Status; Pregnancy; Pregnancy Outcome; Pyridoxine - metabolism; Pyridoxine - therapeutic use; Reproduction - genetics; Reproduction - physiology; Human; Nervous system diseases; Prognosis; Enzyme; Deficiency; Metabolic diseases; Lyases; Cystathionine β-synthase; Enzymopathy; Cerebral disorder; Genetic disease; Pregnancy; Homocystinuria; Reproduction; Treatment; Central nervous system disease; Carbon-oxygen lyases; Fecundity; Aminoacid disorder; Hydro-lyases
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1023/A:1016502408305

Early diagnosis and improved treatment are leading to the potential for increased reproductive capability in homocystinuria due to cystathionine β‐synthase (CβS) 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, CβS 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.