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Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency.

Abstract

Holocarboxylase synthetase is one of two enzymes known to be involved in the metabolism of biotin. It catalyses the fixation of biotin to inactive apocarboxylases yielding active carboxylases. Deficiency of this enzyme leads to multiple carboxylase deficiency which is fatal in the absence of prompt diagnosis and treatment with biotin. In a pregnancy at risk for deficiency of holocarboxylase synthetase prenatal diagnosis was performed by assay of the enzyme in amniocytes. The Km for biotin was 62.8 nM which was 12 times the control value of 5.0 nM. The Vmax was 2 per cent of the control value. This was confirmed by assay of the activity of propionyl CoA carboxylase (20-26 per cent control), 3-methylcrotonyl CoA carboxylase (14-19 per cent control) and pyruvate carboxylase (12-30 per cent control) and demonstration of biotin responsiveness in vitro. All carboxylase activities were restored to 51-58 per cent of control when amniocytes were cultured in medium containing 1 microM biotin. Diagnosis was ultimately confirmed by assay of holocarboxylase synthetase in lymphocytes from the infant after birth. The Km for biotin of the holocarboxylase synthetase of the infant was 60.3 nM while that of a parallel control was 6.9 nM. Prenatal treatment of the mother with biotin led to a concentration of biotin of 240 nM in the serum of the infant at birth that was four times the Km of the enzyme for biotin. The infant was clinically well at birth, and organic acid analysis of the blood and urine revealed no accumulation of the characteristic metabolites.

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  • Authors+Show Affiliations

    ,

    Department of Pediatrics and Institute for Molecular Genetics, University of California, San Diego, La Jolla 92093-0830, USA. thuyle@ucsd.edu

    ,

    Source

    Prenatal diagnosis 19:2 1999 Feb pg 108-12

    MeSH

    Adult
    Amniocentesis
    Biotin
    Carbon-Nitrogen Ligases
    Female
    Fetal Diseases
    Humans
    Infant
    Male
    Multiple Carboxylase Deficiency
    Pregnancy
    Pregnancy Outcome
    Prenatal Diagnosis

    Pub Type(s)

    Case Reports
    Journal Article

    Language

    eng

    PubMed ID

    10215065

    Citation

    Thuy, L P., et al. "Prenatal Diagnosis and Treatment of Holocarboxylase Synthetase Deficiency." Prenatal Diagnosis, vol. 19, no. 2, 1999, pp. 108-12.
    Thuy LP, Belmont J, Nyhan WL. Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. Prenat Diagn. 1999;19(2):108-12.
    Thuy, L. P., Belmont, J., & Nyhan, W. L. (1999). Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. Prenatal Diagnosis, 19(2), pp. 108-12.
    Thuy LP, Belmont J, Nyhan WL. Prenatal Diagnosis and Treatment of Holocarboxylase Synthetase Deficiency. Prenat Diagn. 1999;19(2):108-12. PubMed PMID: 10215065.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. AU - Thuy,L P, AU - Belmont,J, AU - Nyhan,W L, PY - 1999/4/24/pubmed PY - 2000/6/20/medline PY - 1999/4/24/entrez SP - 108 EP - 12 JF - Prenatal diagnosis JO - Prenat. Diagn. VL - 19 IS - 2 N2 - Holocarboxylase synthetase is one of two enzymes known to be involved in the metabolism of biotin. It catalyses the fixation of biotin to inactive apocarboxylases yielding active carboxylases. Deficiency of this enzyme leads to multiple carboxylase deficiency which is fatal in the absence of prompt diagnosis and treatment with biotin. In a pregnancy at risk for deficiency of holocarboxylase synthetase prenatal diagnosis was performed by assay of the enzyme in amniocytes. The Km for biotin was 62.8 nM which was 12 times the control value of 5.0 nM. The Vmax was 2 per cent of the control value. This was confirmed by assay of the activity of propionyl CoA carboxylase (20-26 per cent control), 3-methylcrotonyl CoA carboxylase (14-19 per cent control) and pyruvate carboxylase (12-30 per cent control) and demonstration of biotin responsiveness in vitro. All carboxylase activities were restored to 51-58 per cent of control when amniocytes were cultured in medium containing 1 microM biotin. Diagnosis was ultimately confirmed by assay of holocarboxylase synthetase in lymphocytes from the infant after birth. The Km for biotin of the holocarboxylase synthetase of the infant was 60.3 nM while that of a parallel control was 6.9 nM. Prenatal treatment of the mother with biotin led to a concentration of biotin of 240 nM in the serum of the infant at birth that was four times the Km of the enzyme for biotin. The infant was clinically well at birth, and organic acid analysis of the blood and urine revealed no accumulation of the characteristic metabolites. SN - 0197-3851 UR - https://www.unboundmedicine.com/medline/citation/10215065/Prenatal_diagnosis_and_treatment_of_holocarboxylase_synthetase_deficiency_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0197-3851&date=1999&volume=19&issue=2&spage=108 DB - PRIME DP - Unbound Medicine ER -