Document Detail

Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation.
MedLine Citation:
PMID:  22152680     Owner:  NLM     Status:  MEDLINE    
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.
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:  2013-06-27    
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.
Department of Pediatrics, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
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MeSH Terms
Abnormalities, Multiple / diagnosis,  enzymology,  genetics*
Acidosis, Lactic / genetics
Amino Acid Sequence
Base Sequence
Chromosomes, Human, Pair 4
Energy Metabolism / genetics*
Epilepsy / diagnosis,  enzymology,  genetics*
Escherichia coli / genetics,  growth & development
Fatal Outcome
Fibroblasts / metabolism
Gene Expression
Glycine / blood*,  urine
Infant, Newborn
Infant, Newborn, Diseases / diagnosis,  enzymology,  genetics
Mitochondria / enzymology,  metabolism*
Molecular Sequence Data
Muscle Hypotonia / genetics
Muscle, Skeletal / enzymology
Mutation, Missense
Pyruvate Dehydrogenase Complex / genetics,  metabolism
Sequence Analysis, DNA
Sulfurtransferases / deficiency*
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

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