Prenatal diagnosis of pyruvate carboxylase deficiency by direct measurement of catalytic activity on chorionic villi samples

Abstract

Pyruvate carboxylase (PC) deficiency is a rare metabolic disorder in infants and children, most frequently with fatal outcome. Its prenatal diagnosis by radiometric assay in cultured amniocytes has previously been reported. We present and discuss the prenatal diagnosis of PC deficiency by direct measurement of PC activity in chorionic villi, in two subsequent pregnancies in a family who previously lost a child affected by PC deficiency. In the next pregnancy PC was unmeasurably low in chorionic villi whereas in control samples its activity was between 0·8 and 3·3 nmol min−1 mg protein−1. Following elective termination of the pregnancy PC was shown to be totally inactive in post‐mortem fetal liver. In the most recent pregnancy of the proband's mother PC was normally active in the chorionic villi. The product of this pregnancy was a normal boy. Copyright © 1998 John Wiley & Sons, Ltd.

Prenatal Diagnosis of Disorders of Energy Metabolism

“…This defect has been detected prenatally by enzyme measurement in amniocytes 3 and chorionic villous biopsy. 4 Molecular techniques may supercede this, especially for the First Nation groups in Canada who carry a common PC mutation. Tests for PC deficiency for Caucasian and other groups based on the known gene se-quence is possible but would be much more involved than conventional enzyme assay.…”

Case Report: Prenatal neurological injury in a neonate with pyruvate carboxylase deficiency type B

“…Therefore, this report enriches the pathogenicity variation and phenotype spectrum of the PC gene. In addition to genetic diagnostic tools, direct determination of PC activities in the chorionic villi or cultured amniotic fluid cells in the presence of family history can help prenatally diagnose PCD (15,16). However, when a non-consanguineous couple conceives their first child, PCD is not easily and accurately identified in the prenatal stage.…”

Pyruvate carboxylase deficiency type A and type C: Characterization of five novel pathogenic variants inPCand analysis of the genotype–phenotype correlation

“…We identified an N1081S variant in two patients with type C disease. Since all PCD reports from the pregenome era (Oizumi et al, 1983;Pineda et al, 1995) as well as several others from the genome era (Brun et al, 1999;García-Cazorla et al, 2006;Van Coster et al, 1998) did not describe the pathogenic mutations underlining the phenotypes, any robust hypothesis about genotype-phenotype correlation was difficult.…”

“…Only 38 inactivating mutations in the PC gene have been described in patients with type A and B PCD (Breen et al, 2014;Carbone et al, 1998Carbone et al, , 2002Monnot et al, 2009;Ortez et al, 2013;Wang et al, 2008;Wexler et al, 1998). Several other PCD patients have been reported based on biochemical stigmata of PCD and/or on reduction of pyruvate carboxylase activity, but without molecular confirmation of the diagnosis (Ahmad et al, 1999;Arnold, Griebel, Porterfield, & Brewster, 2001;Brun et al, 1999;Hamilton, Rae, Logan, & Robinson, 1997;Oizumi et al, 1983;Pineda et al, 1995;Robinson et al, 1987;Van Coster, Fernhoff, & De Vivo, 1991;Van Coster, Janssens, Misson, Verloes, & Leroy, 1998).…”