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.
Laboratorio de enfermedades mitocondriales, Centro de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.
Henry
H
Rivera
Begoña
B
Merinero
Mercedes
M
Martinez-Pardo
Ignacio
I
Arroyo
Pedro
P
Ruiz-Sala
Belen
B
Bornstein
Clara
C
Serra-Suhe
Esther
E
Gallardo
Ramon
R
Marti
Maria J
MJ
Moran
Cristina
C
Ugalde
Luis A
LA
Perez-Jurado
Antoni L
AL
Andreu
Rafael
R
Garesse
Magdalena
M
Ugarte
Joaquin
J
Arenas
Miguel A
MA
Martin
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