SCIENTIFIC BACKGROUND

ACADM

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is an autosomal recessively inherited disorder of ß-oxidation of fatty acids. A study of over 930,000 newborns in the U.S. found an incidence of 1:15,000. Previous estimates for the Caucasian population are in the same range. It is probably the most common disorder of fatty acid metabolism of all. The disease is characterized by intolerance to periods of fasting. Homozygous carriers often become ill in infancy after periods of fasting due to viral infections. They typically suffer from repeated vomiting, hypoketotic hypoglycemia, and are lethargic up to comatose. In rare cases, the disease can also lead to sudden infant death syndrome. Biochemical diagnosis can be made by determination of acetylcarnithine in the blood. MCAD deficiency is usually detected as part of newborn screening by tandem mass spectrometry.

 

MCAD deficiency is caused by pathogenic variants in the medium-chain acyl-CoA dehydrogenase gene (ACADM). The most common causative variant, leading to amino acid substitution Lys329Glu, is detectable in approximately 90% of alleles from patients with MCAD deficiency. In most patients this variant is homozygous, in about 1/5 of patients it is present in a combined heterozygous form with another variant. Therapeutically, periods of fasting should be strictly avoided by eating regular meals.

 

References
Matern et al. 2015, GeneReviews® [Internet] / Maier et al. 2009, Hum Mol Genet 18:1612 / Wilcken et al. 2007, Lancet 369:37 / Rhead 2006, J Inherit Metab Dis 29:370 / Derks et al. 2006, Pediatr 148:665

GENES

ACADM

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Cystic fibrosis (CF) is a life-threatening, progressive, inherited condition that causes severe damage to the body, primarily affecting the organs of...

Read more

Down syndrome is a genetic condition caused by the presence of an extra copy of chromosome 21. It affects physical growth, facial features, and cogni...

Read more

Every year on April 25th, DNA Day celebrates the discovery of DNA’s double helix and the advances we’ve made in understanding genetics. D...

Read more

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more

Rosalind Elsie Franklin was a brilliant and meticulous research scientist whose interdisciplinary work made fundamental contributions to various area...

Read more