| Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy. | |
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MedLine Citation:
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PMID: 20453710 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Johan L K Van Hove; Margarita S Saenz; Janet A Thomas; Renata C Gallagher; Mark A Lovell; Laura Z Fenton; Sarah Shanske; Sommer M Myers; Ronald J A Wanders; Jos Ruiter; Marjolein Turkenburg; Hans R Waterham |
Publication Detail:
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Type: Case Reports; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Pediatric research Volume: 68 ISSN: 1530-0447 ISO Abbreviation: Pediatr. Res. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-15 Completed Date: 2010-10-08 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 159-64 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, University of Colorado Denver, Aurora, Colorado 80045, USA. Vanhove.Johan@tchden.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Base Sequence Brain / metabolism, pathology Brain Diseases, Metabolic* / enzymology, genetics, pathology DNA Mutational Analysis Fatal Outcome Female Humans Infant Infant, Newborn Leigh Disease / enzymology, genetics, pathology Liver Diseases* / enzymology, genetics, pathology Magnetic Resonance Imaging Mitochondrial Diseases* / enzymology, genetics, pathology Molecular Sequence Data Mutation Succinate-CoA Ligases / deficiency*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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U01 DK062453/DK/NIDDK NIH HHS; U54 DK078377/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 6.2.1.-/Succinate-CoA Ligases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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