Marked mitochondrial DNA depletion associated with a novel SUCLG1 gene mutation resulting in lethal neonatal acidosis, multi-organ failure, and interrupted aortic arch.
The aim of this study was to identify the causative genetic lesion in two apparently unrelated newborns having lethal lactic acidosis, multi-organ failure and congenital malformations including interrupted aortic arch, who exhibited mild methylmalonic aciduria, combined mitochondrial respiratory chain deficiency, and marked muscle mitochondrial DNA depletion. A novel mutation in the SUCLG1 gene was identified. Phenotype severity in Succinate-CoA ligase dysfunction appears to be more correlated to the muscle mtDNA content than to the tissue distribution of the heterodimer subunits. Prominent impairment of mitochondrial respiratory chain may result in deep ravages in developmental tissues leading to multiple organ failure and malformations.
Rivera
Henry
H
Laboratorio de enfermedades mitocondriales, Centro de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.
Merinero
Begoña
B
Martinez-Pardo
Mercedes
M
Arroyo
Ignacio
I
Ruiz-Sala
Pedro
P
Bornstein
Belen
B
Serra-Suhe
Clara
C
Gallardo
Esther
E
Marti
Ramon
R
Moran
Maria J
MJ
Ugalde
Cristina
C
Perez-Jurado
Luis A
LA
Andreu
Antoni L
AL
Garesse
Rafael
R
Ugarte
Magdalena
M
Arenas
Joaquin
J
Martin
Miguel A
MA
D000138:Acidosis / Q000235:genetics*; D001013:Aorta, Thoracic / Q000002:abnormalities*; D004272:DNA, Mitochondrial / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine; D024101:Mitochondrial Proteins / Q000172:deficiency*; D009102:Multiple Organ Failure / Q000151:congenital* / Q000235:genetics; D009132:Muscles / Q000473:pathology; D020125:Mutation, Missense; D013389:Succinate-CoA Ligases / Q000172:deficiency*
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D008764:Methylmalonic Acid; D013389:Succinate-CoA Ligases