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

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Journal of Inherited Metabolic Disease

Abstract

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.

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Authors and Affiliations

  1. Division of Genetics, Children's Hospital, Departments of Pediatrics and Boston, Massachusetts

    J. E. Vargas & S. E. Waisbren

  2. Psychiatry, Harvard Medical School, Boston, Massachusetts

    S. E. Waisbren

  3. Departments of Pediatrics, Pathology, Obstetrics and Gynecology, and Medicine, Medical College of Ohio, Toledo, Ohio

    T. W. Kurczynski

  4. Valley Children's Hospital/UCSF, Madera, California

    E. R. Roeder

  5. Division of Human Genetics and Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut

    R. S. Schwartz

  6. Connecticut Children's Medical Center, Hartford, Connecticut, USA

    S. Rosengren

  7. Section on Genetics and Metabolism, Departments of Pediatrics, Child Health, Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba

    C. Prasad & C. R. Greenberg

  8. Division of Medical Genetics, MUHC–Royal Victoria Hospital, Montreal, Quebec

    B. M. Gilfix

  9. Memorial University, Newfoundland, Canada

    D. MacGregor

  10. Massachusetts General Hospital and the Department of Neurology, Harvard Medical School, Boston, Massachusetts

    V. E. Shih

  11. Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA

    L. Bao & J. P. Kraus

  12. Children's Hospital, 300 Longwood Avenue, IC-106, Boston, MA, 02115, USA

    H. L. Levy

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  1. H. L. Levy
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  2. J. E. Vargas
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  3. S. E. Waisbren
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  4. T. W. Kurczynski
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  5. E. R. Roeder
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  6. R. S. Schwartz
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  7. S. Rosengren
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  8. C. Prasad
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  9. C. R. Greenberg
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  10. B. M. Gilfix
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  11. D. MacGregor
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  12. V. E. Shih
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  13. L. Bao
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  14. J. P. Kraus
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Correspondence to H. L. Levy.

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Levy, H.L., Vargas, J.E., Waisbren, S.E. et al. Reproductive fitness in maternal homocystinuria due to cystathionine β-synthase deficiency. J Inherit Metab Dis 25, 299–314 (2002). https://doi.org/10.1023/A:1016502408305

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