| Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation. | |
| | |
MedLine Citation:
|
PMID: 22152680 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Lipoic acid is an essential prosthetic group of four mitochondrial enzymes involved in the oxidative decarboxylation of pyruvate, α-ketoglutarate, and branched chain amino acids and in the glycine cleavage. Lipoic acid is synthesized stepwise within mitochondria through a process that includes lipoic acid synthetase. We identified the homozygous mutation c.746G>A (p.Arg249His) in LIAS in an individual with neonatal-onset epilepsy, muscular hypotonia, lactic acidosis, and elevated glycine concentration in plasma and urine. Investigation of the mitochondrial energy metabolism showed reduced oxidation of pyruvate and decreased pyruvate dehydrogenase complex activity. A pronounced reduction of the prosthetic group lipoamide was found in lipoylated proteins. |
| | |
Authors:
|
Johannes A Mayr; Franz A Zimmermann; Christine Fauth; Christa Bergheim; David Meierhofer; Doris Radmayr; Johannes Zschocke; Johannes Koch; Wolfgang Sperl |
Publication Detail:
|
Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: American journal of human genetics Volume: 89 ISSN: 1537-6605 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-13 Completed Date: 2012-02-02 Revised Date: 2012-06-19 |
Medline Journal Info:
|
Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
|
Languages: eng Pagination: 792-7 Citation Subset: IM |
Copyright Information:
|
Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Pediatrics, Paracelsus Medical University Salzburg, Salzburg 5020, Austria. h.mayr@salk.at |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Abnormalities, Multiple
/
diagnosis,
enzymology,
genetics* Acidosis, Lactic / genetics Amino Acid Sequence Base Sequence Chromosomes, Human, Pair 4 Consanguinity Energy Metabolism / genetics* Epilepsy / diagnosis, enzymology, genetics* Escherichia coli / genetics, growth & development Fatal Outcome Fibroblasts / metabolism Gene Expression Glycine / blood*, urine Homozygote Humans Infant, Newborn Infant, Newborn, Diseases / diagnosis, enzymology, genetics Male Mitochondria / enzymology, metabolism* Molecular Sequence Data Muscle Hypotonia / genetics Muscle, Skeletal / enzymology Mutation, Missense Pyruvate Dehydrogenase Complex / genetics, metabolism Sequence Analysis, DNA Sulfurtransferases / deficiency* |
| Chemical | |
Reg. No./Substance:
|
0/Pyruvate Dehydrogenase Complex; 56-40-6/Glycine; EC 2.8.1.-/Sulfurtransferases; EC 2.8.1.-/lipoic acid synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequenci...
Next Document: Dissecting the genetics of complex inheritance: linkage disequilibrium mapping provides insight into...