New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria.
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.
Valayannopoulos
Vassili
V
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.
Haudry
Coralie
C
Serre
Valérie
V
Barth
Magalie
M
Boddaert
Nathalie
N
Arnoux
Jean-Baptiste
JB
Cormier-Daire
Valérie
V
Rio
Marlène
M
Rabier
Daniel
D
Vassault
Anne
A
Munnich
Arnold
A
Bonnefont
Jean-Paul
JP
de Lonlay
Pascale
P
Rötig
Agnès
A
Lebre
Anne-Sophie
AS
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*
D024101:Mitochondrial Proteins; D008764:Methylmalonic Acid; D013389:Succinate-CoA Ligases; D002331:Carnitine