title: New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria.
abstract: Deficiencies in two subunits of the succinyl-coenzyme A synthetase (SCS) have been involved in patients with encephalomyopathy and mild methylmalonic aciduria (MMA). In this study, we described three new SUCLG1 patients and performed a meta-analysis of the literature. Our report enlarges the phenotypic spectrum of SUCLG1 mutations and confirms that a characteristic metabolic profile (presence of MMA and C4-DC carnitine in urines) and basal ganglia MRI lesions are the hallmarks of SCS defects. As mitochondrial DNA depletion in muscle is not a constant finding in SUCLG1 patients, this may suggest that diagnosis should not be based on it, but also that alternative physiopathological mechanisms may be considered to explain the combined respiratory chain deficiency observed in SCS patients.
authors.affiliation: Université Paris Descartes, Hôpital Necker-Enfants Malades et Inserm U781 et U797, Départements de Génétique, de Radiologie pédiatrique, des Maladies Métaboliques et de Biochimie B, Paris F-75015, France.
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Coralie
authors.initials: C
authors.lastname: Haudry
authors.forename: Valérie
authors.initials: V
authors.lastname: Serre
authors.forename: Magalie
authors.initials: M
authors.lastname: Barth
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Arnoux
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabier
authors.forename: Anne
authors.initials: A
authors.lastname: Vassault
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Agnès
authors.initials: A
authors.lastname: Rötig
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lebre
mesh_terms: D000293:Adolescent; D000818:Animals; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000473:pathology; D002331:Carnitine / Q000031:analogs & derivatives / Q000652:urine; D002648:Child; D002675:Child, Preschool; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine; D024101:Mitochondrial Proteins / Q000172:deficiency*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011859:Radiography; D013389:Succinate-CoA Ligases / Q000172:deficiency*
chemical_list: D024101:Mitochondrial Proteins; D008764:Methylmalonic Acid; D013389:Succinate-CoA Ligases; D002331:Carnitine