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.

Dessein, Anne-Frédérique

Fontaine, Monique

Andresen, Brage S

Gregersen, Niels

Brivet, Michèle

Rabier, Daniel

Napuri-Gouel, Silvia

Dobbelaere, Dries

Mention-Mulliez, Karine

Martin-Ponthieu, Annie

Briand, Gilbert

Millington, David S

Vianey-Saban, Christine

Wanders, Ronald JA

Vamecq, Joseph

England

2011-06-21T17:30:25Z

2010-10-05

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.

Version of Record

http://www.ncbi.nlm.nih.gov/pubmed/20923556

1750-1172-5-26

1750-1172

https://hdl.handle.net/10161/4385

eng

en_US

Springer Science and Business Media LLC

Orphanet J Rare Dis

10.1186/1750-1172-5-26

Orphanet Journal of Rare Diseases

Acyl-CoA Dehydrogenase

Adult

Carnitine

Cells, Cultured

Child, Preschool

Deficiency Diseases

Fatty Acids

Female

Fibroblasts

Genetic Predisposition to Disease

Humans

Lymphocytes

Male

Mutation

Oxidation-Reduction

Pedigree

Polymerase Chain Reaction

Skin

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.

Journal article

2010-10-5

5

http://www.ncbi.nlm.nih.gov/pubmed/20923556

26

Clinical Science Departments

Duke

Pediatrics

Pediatrics, Medical Genetics

School of Medicine

Published online

5