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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2010

Open Access 01-12-2010 | Research

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

Authors: Anne-Frédérique Dessein, Monique Fontaine, Brage S Andresen, Niels Gregersen, Michèle Brivet, Daniel Rabier, Silvia Napuri-Gouel, Dries Dobbelaere, Karine Mention-Mulliez, Annie Martin-Ponthieu, Gilbert Briand, David S Millington, Christine Vianey-Saban, Ronald JA Wanders, Joseph Vamecq

Published in: Orphanet Journal of Rare Diseases | Issue 1/2010

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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.
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Metadata
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
Authors
Anne-Frédérique Dessein
Monique Fontaine
Brage S Andresen
Niels Gregersen
Michèle Brivet
Daniel Rabier
Silvia Napuri-Gouel
Dries Dobbelaere
Karine Mention-Mulliez
Annie Martin-Ponthieu
Gilbert Briand
David S Millington
Christine Vianey-Saban
Ronald JA Wanders
Joseph Vamecq
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2010
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-5-26

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