Show simple item record Dessein, AF Fontaine, M Andresen, BS Gregersen, N Brivet, M Rabier, D Napuri-Gouel, S Dobbelaere, D Mention-Mulliez, K Martin-Ponthieu, A Briand, G Millington, DS Vianey-Saban, C Wanders, RJ Vamecq, J
dc.coverage.spatial England 2011-06-21T17:30:25Z 2010-10-05
dc.identifier 1750-1172-5-26
dc.identifier.citation Orphanet J Rare Dis, 2010, 5 pp. 26 - ?
dc.description.abstract A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.
dc.format.extent 26 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof Orphanet J Rare Dis
dc.relation.isversionof 10.1186/1750-1172-5-26
dc.subject Acyl-CoA Dehydrogenase
dc.subject Adult
dc.subject Carnitine
dc.subject Cells, Cultured
dc.subject Child, Preschool
dc.subject Deficiency Diseases
dc.subject Fatty Acids
dc.subject Female
dc.subject Fibroblasts
dc.subject Genetic Predisposition to Disease
dc.subject Humans
dc.subject Lymphocytes
dc.subject Male
dc.subject Mutation
dc.subject Oxidation-Reduction
dc.subject Pedigree
dc.subject Polymerase Chain Reaction
dc.subject Skin
dc.title A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency: a case report.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-10-5 en_US
duke.description.endpage 26 en_US
duke.description.issue en_US
duke.description.startpage 26 en_US
duke.description.volume 5 en_US
dc.relation.journal Orphanet Journal of Rare Diseases en_US
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics/Pediatrics, Medical Genetics
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 1750-1172

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