Succinyl-CoA Ligase Deficiency: A Mitochondrial Hepatoencephalomyopathy
Open Access
- 1 August 2010
- journal article
- case report
- Published by Springer Science and Business Media LLC in Pediatric Research
- Vol. 68 (2), 159-164
- https://doi.org/10.1203/pdr.0b013e3181e5c3a4
Abstract
This patient presented on the first day of life with pronounced lactic acidosis with an elevated lactate/pyruvate ratio. Urine organic acids showed Krebs cycle metabolites and mildly elevated methylmalonate and methylcitrate. The acylcarnitine profile showed elevated propionylcarnitine and succinylcarnitine. Amino acids showed elevated glutamic acid, glutamine, proline, and alanine. From the age 2 of mo on, she had elevated transaminases and intermittent episodes of liver failure. Liver biopsy showed steatosis and a decrease of mitochondrial DNA to 50% of control. She had bilateral sensorineural hearing loss. Over the course of the first 2 y of life, she developed a progressively severe myopathy with pronounced muscle weakness eventually leading to respiratory failure, Leigh disease, and recurrent hepatic failure. The hepatic symptoms and the metabolic parameters temporarily improved on treatment with aspartate, but neither muscle symptoms nor brain lesions improved. Laboratory testing revealed a deficiency of succinyl-CoA ligase enzyme activity and protein in fibroblasts because of a novel homozygous mutation in the SUCLG1 gene: c.40A>T (p.M14L). Functional analysis suggests that this methionine is more likely to function as the translation initiator methionine, explaining the pathogenic nature of the mutation. Succinyl-CoA ligase deficiency due to an SUCLG1 mutation is a new cause for mitochondrial hepatoencephalomyopathy.Keywords
This publication has 20 references indexed in Scilit:
- Succinyl-CoA Synthetase Is a Phosphate Target for the Activation of Mitochondrial MetabolismBiochemistry, 2009
- A novel missense mutation in SUCLG1 associated with mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduriaEuropean Journal of Pediatrics, 2009
- Deficiency of the α Subunit of Succinate–Coenzyme A Ligase Causes Fatal Infantile Lactic Acidosis with Mitochondrial DNA DepletionAmerican Journal of Human Genetics, 2007
- Depletion of mtDNA: Syndromes and genesMitochondrion, 2007
- Early nonsense: mRNA decay solves a translational problemNature Reviews Molecular Cell Biology, 2006
- Aberrant termination triggers nonsense-mediated mRNA decayBiochemical Society Transactions, 2006
- Aberrant termination triggers nonsense-mediated mRNA decayBiochemical Society Transactions, 2006
- Expression of Two Succinyl-CoA Synthetases with Different Nucleotide Specificities in Mammalian TissuesOnline Journal of Public Health Informatics, 2004
- Characterization of the ATP- and GTP-specific Succinyl-CoA Synthetases in PigeonOnline Journal of Public Health Informatics, 1998
- Computational Method to Predict Mitochondrially Imported Proteins and their Targeting SequencesJBIC Journal of Biological Inorganic Chemistry, 1996