Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy.

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Van Hove JL, Saenz MS, Thomas JA, Gallagher RC, Lovell MA, Fenton LZ, Shanske S, Myers SM, Wanders RJ, Ruiter J, Turkenburg M, Waterham HR

Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy.

Pediatr Res. 2010 Aug;68(2):159-64. doi: 10.1203/00006450-201011001-00310.

PubMed ID

20453710 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Succinic acid	Succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrial	Protein	Humans	Unknown	Product of	Details

Polypeptides

Name	UniProt ID
Succinyl-CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial	P53597	Details