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 reportReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Orphanet Journal of Rare Diseases

, 5:26

First Online: 05 October 2010Received: 13 April 2010Accepted: 05 October 2010DOI: 10.1186-1750-1172-5-26

Cite this article as: Dessein, AF., Fontaine, M., Andresen, B.S. et al. Orphanet J Rare Dis 2010 5: 26. doi:10.1186-1750-1172-5-26

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-C-octanoate and 9, 10-H-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.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-1172-5-26 contains supplementary material, which is available to authorized users.

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Autor: Anne-Frédérique Dessein - Monique Fontaine - Brage S Andresen - Niels Gregersen - Michèle Brivet - Daniel Rabier - Silvi

Fuente: https://link.springer.com/







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