Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (OMIM 201450) is the most common inherited disorder of fatty acid metabolism presenting with hypoglycaemia, hepatopathy and Reye-like symptoms during catabolism. In the past, the majority of patients carried the prevalent c.985A>G mutation in...

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Autores principales:	Marga Sturm, Diran Herebian, Martina Mueller, Maurice D Laryea, Ute Spiekerkoetter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e488ed6eedc74f2f86850021d402f2e8
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spelling	oai:doaj.org-article:e488ed6eedc74f2f86850021d402f2e82021-11-18T07:05:23ZFunctional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.1932-620310.1371/journal.pone.0045110https://doaj.org/article/e488ed6eedc74f2f86850021d402f2e82012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028790/?tool=EBIhttps://doaj.org/toc/1932-6203Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (OMIM 201450) is the most common inherited disorder of fatty acid metabolism presenting with hypoglycaemia, hepatopathy and Reye-like symptoms during catabolism. In the past, the majority of patients carried the prevalent c.985A>G mutation in the ACADM gene. Since the introduction of newborn screening many other mutations with unknown clinical relevance have been identified in asymptomatic newborns. In order to identify functional effects of these mutant genotypes we correlated residual MCAD (OMIM 607008) activities as measured by octanoyl-CoA oxidation in lymphocytes with both genotype and relevant medical reports in 65 newborns harbouring mutant alleles. We identified true disease-causing mutations with residual activities of 0 to 20%. In individuals carrying the c.199T>C or c.127G>A mutation on one allele, residual activities were much higher and in the range of heterozygotes (31%-60%). Therefore, both mutations cannot clearly be associated with a clinical phenotype. This demonstrates a correlation between the octanoyl-CoA oxidation rate in lymphocytes and the clinical outcome. With newborn screening, the natural course of disease is difficult to assess. The octanoyl-CoA oxidation rate, therefore, allows a risk assessment at birth and the identification of new ACADM genotypes associated with asymptomatic disease variants.Marga SturmDiran HerebianMartina MuellerMaurice D LaryeaUte SpiekerkoetterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45110 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marga Sturm Diran Herebian Martina Mueller Maurice D Laryea Ute Spiekerkoetter Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.
description	Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (OMIM 201450) is the most common inherited disorder of fatty acid metabolism presenting with hypoglycaemia, hepatopathy and Reye-like symptoms during catabolism. In the past, the majority of patients carried the prevalent c.985A>G mutation in the ACADM gene. Since the introduction of newborn screening many other mutations with unknown clinical relevance have been identified in asymptomatic newborns. In order to identify functional effects of these mutant genotypes we correlated residual MCAD (OMIM 607008) activities as measured by octanoyl-CoA oxidation in lymphocytes with both genotype and relevant medical reports in 65 newborns harbouring mutant alleles. We identified true disease-causing mutations with residual activities of 0 to 20%. In individuals carrying the c.199T>C or c.127G>A mutation on one allele, residual activities were much higher and in the range of heterozygotes (31%-60%). Therefore, both mutations cannot clearly be associated with a clinical phenotype. This demonstrates a correlation between the octanoyl-CoA oxidation rate in lymphocytes and the clinical outcome. With newborn screening, the natural course of disease is difficult to assess. The octanoyl-CoA oxidation rate, therefore, allows a risk assessment at birth and the identification of new ACADM genotypes associated with asymptomatic disease variants.
format	article
author	Marga Sturm Diran Herebian Martina Mueller Maurice D Laryea Ute Spiekerkoetter
author_facet	Marga Sturm Diran Herebian Martina Mueller Maurice D Laryea Ute Spiekerkoetter
author_sort	Marga Sturm
title	Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.
title_short	Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.
title_full	Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.
title_fullStr	Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.
title_full_unstemmed	Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.
title_sort	functional effects of different medium-chain acyl-coa dehydrogenase genotypes and identification of asymptomatic variants.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e488ed6eedc74f2f86850021d402f2e8
work_keys_str_mv	AT margasturm functionaleffectsofdifferentmediumchainacylcoadehydrogenasegenotypesandidentificationofasymptomaticvariants AT diranherebian functionaleffectsofdifferentmediumchainacylcoadehydrogenasegenotypesandidentificationofasymptomaticvariants AT martinamueller functionaleffectsofdifferentmediumchainacylcoadehydrogenasegenotypesandidentificationofasymptomaticvariants AT mauricedlaryea functionaleffectsofdifferentmediumchainacylcoadehydrogenasegenotypesandidentificationofasymptomaticvariants AT utespiekerkoetter functionaleffectsofdifferentmediumchainacylcoadehydrogenasegenotypesandidentificationofasymptomaticvariants
_version_	1718424011891802112

Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.

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