Disorder of intracellular cobalamin metabolism: Importance of rapid diagnostic illustrated by a case report of early-onset methylmalonic aciduria and homocystinuria, cobalamin C type
Etienne Mondesert,
Bastien Baud,
Agathe Roubertie,
Jean-François Benoist,
Pierre-Edouard Grillet,
Jean-Paul Cristol,
Marie Céline Francois-Heude,
Manuel Schiff,
Stéphanie Badiou
Affiliations
Etienne Mondesert
Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; Institute for Neurosciences of Montpellier, University of Montpellier, INSERM U 1298, Montpellier, France; Corresponding author. Department of Biochemistry, Lapeyronie Hospital, Montpellier, F34295, France.
Bastien Baud
Department of Biochemistry, University Hospital of Montpellier, Montpellier, France
Agathe Roubertie
Institute for Neurosciences of Montpellier, University of Montpellier, INSERM U 1298, Montpellier, France; Department of Pediatric Neurology, University Hospital of Montpellier, Montpellier, France
Jean-François Benoist
Department of Biochemistry, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Paris-Saclay, Paris, France
Pierre-Edouard Grillet
Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; PhyMedExp, Université de Montpellier (UM), Inserm, CNRS, Montpellier, France
Jean-Paul Cristol
Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; PhyMedExp, Université de Montpellier (UM), Inserm, CNRS, Montpellier, France
Marie Céline Francois-Heude
Institute for Neurosciences of Montpellier, University of Montpellier, INSERM U 1298, Montpellier, France
Manuel Schiff
Reference Center for Inborn Errors of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris cité, Paris, France
Stéphanie Badiou
Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; PhyMedExp, Université de Montpellier (UM), Inserm, CNRS, Montpellier, France
Methylmalonic aciduria and homocystinuria, cobalamin C type (cblC), constitute the most common inborn error of intracellular cobalamin metabolism. Here, we report the case of a 6-month-old child, presenting severe subacute neurological decline associated with failure to thrive. Biochemical tests indicated a disorder of intracellular cobalamin metabolism, with elevated urinary and plasma methylmalonic acid levels associated with high plasma homocysteine concentrations, with normal plasma vitamin B12 concentrations. Diagnosis was later confirmed by genetic analysis which identified two pathogenic variants on the MMACHC gene: c.271dupA (p.Arg91lysfs∗14) paternal allele and c.388T > C (p.Tyr130His) maternal allele. The patient responded well to hydroxocobalamin treatment, with a rapid recovery of symptoms and a normal growth at 2.8 years of follow-up. This case illustrates the importance of early diagnosis of cobalamin metabolism disorders by prescribing adequate biochemical tests.
