Prenatal diagnosis of medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency in a family with a previous fatal case of sudden unexpected death in childhood

  title={Prenatal diagnosis of medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency in a family with a previous fatal case of sudden unexpected death in childhood},
  author={N. Gregersen and Vibeke Winter and Peter Kryger Jensen and Anni Holmskov and S. Kolvraa and Brage Storstein Andresen and Ernst Christensen and Peter Bross and Jytte Banner Lundemose and Markil Gregersen},
  journal={Prenatal Diagnosis},
Medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited disease with a carrier frequency of approximately 1:100 in most Caucasian populations. The disease is implicated in sudden unexpected death in childhood. A prevalent disease‐causing point mutation (A985G) in the MCAD gene has been characterized, thus rendering diagnosis easy in the majority of cases. Since the clinical spectrum of MCAD deficiency ranges from death in the first days of life to an asymptomatic… 
Frequency of 985A‐to‐G mutation in medium‐chain acyl‐CoA dehydrogenase gene among patients with sudden infant death syndrome, Reye syndrome, severe motor and intellectual disabilities and healthy newborns in Japan
  • M. Nagao
  • Medicine
    Acta paediatrica Japonica : Overseas edition
  • 1996
The result of the present study accord with previous reports that MCAD deficiency is a common disorder in Caucasians, but quite rare among Japanese, and newborn mass‐screening for MCad deficiency using this method will not be practical in Japan.
DNA-based prenatal diagnosis for very-long- chain acyl-CoA dehydrogenase deficiency
A fast and reliable method for PCR amplification and direct sequencing of the entire VLCAD coding region from genomic DNA is established and used to identify 58 different disease-causing mutations in 55 unrelated families, thereby enabling DNA-based prenatal diagnosis.
Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl‐CoA dehydrogenase deficiencies, with special focus on genotype–phenotype relationship
It is proposed that the unraveling of the genetic and cellular determinants of the modulating effects of protein quality control systems may help to assess the balance between genetic and environmental factors in the clinical expression of a given mutation.
Fatty acid oxidation disorders as primary cause of sudden and unexpected death in infants and young children: an investigation performed on cultured fibroblasts from 79 children who died aged between 0-4 years.
The results indicate that disorders of fatty acid oxidation play a small but significant role in the cause of unexpected death in infants and young children, and that infants and children dying in this way should be regarded as high risk candidates for metabolic diseases.
Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried postmortem blood specimens collected at autopsy from infants with unexplained cause of death.
MS/MS is cost-effective for analysis of postmortem specimens and should be considered for routine use by Medical Examiners and pathologists in unexpected/unknown infant and child death.
Liver Disease in Children: Inborn Errors of Mitochondrial Fatty Acid Oxidation
FAO disorders have become an important group of inherited metabolic disorders causing morbidity and mortality and may cause sudden unexpected death if unrecognized and untreated.
Metabolic basis of pediatric heart disease


The frequency of a disease‐causing point mutation in the gene coding for medium‐chain acyl‐CoA dehydrogenase in sudden infant death syndrome
No over‐representation of homo‐ or heterozygosity‐for G985 appears to exist in such a strictly defined population, for which reason it may be relevant to look at a broader spectrum of clinical presentations of inherited metabolic disorders and examine a wider range of sudden death in infancy.
Frequency of Medium-Chain Acyl-CoA Dehydrogenase Deficiency G-985 Mutation in Sudden Infant Death Syndrome
It is concluded that the specific MCad deficiency mutation G-985 is not strongly associated with SIDS and that MCAD deficiency probably does not make a significant contribution to the etiology of SIDS.
A rare disease-associated mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene changes a conserved arginine, previously shown to be functionally essential in short-chain acyl-CoA dehydrogenase (SCAD).
It is suggested that the T157 mutation destroys a salt bridge between arginine28 and glutamate86, thereby affecting the formation of enzymatically active protein in medium-chain acyl-CoA dehydrogenase.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: the prevalent mutation G985 (K304E) is subject to a strong founder effect from northwestern Europe.
The results support the notion of a founder effect in northwestern Europe by showing that MCAD deficiency due to the G985 mutation is more frequent in the Netherlands, Ireland, England, Belgium and Denmark than in other western European countries.
Sudden child death and 'healthy' affected family members with medium-chain acyl-coenzyme A dehydrogenase deficiency.
It is suggested that a deficiency of medium-chain acyl-coenzyme A dehydrogenase may lead to a life-threatening illness when other complicating factors such as diarrhea and vomiting result in an abnormal depletion of the body's glycogen stores.
Mutations in the medium chain acyl‐CoA dehydrogenase (MCAD) gene
In the compilation of data from a worldwide study of 172 unrelated patients each representing an independent pedigree, a total of 8 different mutations have been identified, and a single prevalent mutation, 985A→G, was found in 90% of 344 variant alleles.