Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency

G. A. Mitchell, C. Jakobs, K. M. Gibson, M. F. Robert, A. Burlina, C. Dionisi-Vici, L. Dallaire

Research output: Contribution to journalArticle

Abstract

We report the first molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency. The proband had a classic but severe presentation with hypoketotic hypoglycaemia and acidosis, secondary mental retardation, and epilepsy, and HL deficiency was documented in cultured fibroblasts. We found him to be homozygous for the frameshift mutation N46fs (+ 1), which yields a distinct pattern on single-strand conformation polymorphism (SSCP) analysis. In two subsequent pregnancies, molecular prenatal diagnosis was performed using SSCP. In the first, chorionic villus biopsy was normal. In the second pregnancy, amniocentesis revealed an affected fetus. In both pregnancies, the diagnosis was confirmed enzymatically. HL activity was less than 7 per cent of control values in amniocytes and fetal liver of the affected pregnancy. In the second pregnancy, amniotic fluid metabolite measurements by stable isotope dilution-selected ion monitoring mass spectrometry showed greater than 100-fold increases of 3-hydroxy-3-methylglutaric acid and of 3-methylglutaconic acid levels compared with controls.

Original languageEnglish
Pages (from-to)725-729
Number of pages5
JournalPrenatal Diagnosis
Volume15
Issue number8
DOIs
Publication statusPublished - 1995

Fingerprint

Prenatal Diagnosis
Pregnancy
Meglutol
Chorionic Villi Sampling
Frameshift Mutation
Amniocentesis
Amniotic Fluid
Acidosis
Hypoglycemia
Isotopes
Intellectual Disability
Epilepsy
Mass Spectrometry
Fetus
Fibroblasts
3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
Ions
Liver

Keywords

  • Amino acid metabolism
  • Clone
  • Hydroxymethylglutaryl CoA lyase
  • Inborn errors
  • Ketoacid lyases
  • Prenatal

ASJC Scopus subject areas

  • Genetics(clinical)
  • Obstetrics and Gynaecology

Cite this

Mitchell, G. A., Jakobs, C., Gibson, K. M., Robert, M. F., Burlina, A., Dionisi-Vici, C., & Dallaire, L. (1995). Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency. Prenatal Diagnosis, 15(8), 725-729. https://doi.org/10.1002/pd.1970150807

Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency. / Mitchell, G. A.; Jakobs, C.; Gibson, K. M.; Robert, M. F.; Burlina, A.; Dionisi-Vici, C.; Dallaire, L.

In: Prenatal Diagnosis, Vol. 15, No. 8, 1995, p. 725-729.

Research output: Contribution to journalArticle

Mitchell, GA, Jakobs, C, Gibson, KM, Robert, MF, Burlina, A, Dionisi-Vici, C & Dallaire, L 1995, 'Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency', Prenatal Diagnosis, vol. 15, no. 8, pp. 725-729. https://doi.org/10.1002/pd.1970150807
Mitchell, G. A. ; Jakobs, C. ; Gibson, K. M. ; Robert, M. F. ; Burlina, A. ; Dionisi-Vici, C. ; Dallaire, L. / Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency. In: Prenatal Diagnosis. 1995 ; Vol. 15, No. 8. pp. 725-729.
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