View source for Medium-chain acyl-coenzyme A dehydrogenase deficiency

{{DiseaseDisorder infobox |
  Name           = Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD) |
  ICD10          = |
  ICD9           = {{ICD9|277.85}} |
  ICDO           = |
  Image          = |
  Caption        = |
  OMIM           = 201450 |
  MedlinePlus    = |
  eMedicineSubj  = ped |
  eMedicineTopic = 1392 |
  DiseasesDB     = |
}}
{{SI}}


'''Medium-chain acyl-coenzyme A dehydrogenase deficiency''' is one of a group of conditions that is associated with [[inborn error of metabolism|inborn errors of metabolism]] in [[fatty acid]] [[oxidation]]. It is due to defects in the [[enzyme]] complex known as ''medium-chain acyl dehydrogenase'' (MCAD) and reduced activity of this complex. 

It is recognised as one of the rarer causes of [[sudden infant death syndrome]] (SIDS, "cot death" or "crib death"); although it is better described as a mimic, rather than a cause, of SIDS.

==Background==
Two main types of fat are found in the body: [[triglyceride]]s and [[wax]]es.  A triglyceride consists of a three-carbon compound known as [[glycerol]] to which three fatty acids ([[carboxylic acid]]s) are attached by [[ester]] bonds. Triglycerides occur in living things with fatty acids of different lengths. These may be divided into very long-chain, long-chain, medium-chain or short-chain depending on the number of carbon atoms that are present.

==Metabolic enzymes==
The fatty acids are broken down in stages by the successive removal of small molecules containing 2 carbon atoms. Ultimately, under normal conditions, the fatty acids are converted into [[carbon dioxide]] and [[water]] with the liberation of energy during this process. A complex of seven enzymes is required to remove each 2-carbon molecule. As the process involves removal of hydrogen atoms (i.e. an oxidation) from an [[Acyl|acyl group]], the enzyme complex is known as an acyl [[dehydrogenase]]. Different enzymes are required to hold fatty acids of different lengths, and the deficiencies connected with these various proteins are: 
*[[Very long-chain acyl-coenzyme A dehydrogenase deficiency]] (VLCAD)
*[[Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency]] (LCAD)
*[[Medium-chain acyl-coenzyme A dehydrogenase deficiency]] (MCAD)
*[[Short-chain acyl-coenzyme A dehydrogenase deficiency]] (SCAD)

In individuals that have reduced activity of MCAD there is an impairment of fatty acid oxidation. Under conditions of health this may not cause significant problems. However, when such individuals become unwell for some other reason, the impairment of fatty acid oxidation may lead to [[hypoglycemia]], [[hyperammonemia]] and, possibly, sudden death. 

The oxidation of fatty acids occurs within [[mitochondria]]. Fatty acids from the [[cytoplasm]] are attached to a molecule called [[carnitine]] to transport them across the mitochondrial membrane. The combination of carnitine with a fatty acid is known as acyl carnitine. In individuals with MCAD deficiency, there is an increase in the [[concentration]] of medium-chain acyl carnitines in the cytoplasm of their cells; these acyl carnitines leak into the blood stream.

==Investigation of "cot death"==
During the course of an investigation of an infant that has suffered a "cot death", a sample of blood may be taken to measure the concentration of acyl carnitines. MCAD deficiency may be inferred when the levels of acyl carnitines in the blood are raised in a typical pattern. 

If the interval between "cot death" and post-mortem examination ([[autopsy]]) is not too long, it is sometimes possible to culture cells called [[fibroblasts]] from the dermis of a sample of [[skin]] taken during the course of the examination. It is possible to add fatty acids that contain [[radioactive]] carbon atoms ([[carbon-14]]) to the culture medium. If the cells oxidise these fatty acids during the course of their metabolism, radioactive carbon dioxide will be produced, which may be detected using suitable apparatus. The rate of production of radioactive carbon dioxide from fatty acid chains of differing lengths may be used as a test to evaluate whether the cells have a deficiency in any of the various acyl dehydrogenases. This type of test may be used to support a diagnosis of MCAD deficiency when it is suspected from the pattern of acyl carnitines in the blood.
[[Image:autorecessive.jpg|thumb|left|250px|Medium-chain acyl-coenzyme A dehydrogenase deficiency is inherited in an [[Recessive gene|autosomal recessive]] pattern.]]
The diagnosis of MCAD deficiency should also be considered in the presence of prominent fatty change (also known as [[steatosis]]) within the [[liver]] and proximal renal tubules of the [[kidney]]. However, steatosis is recognised as a non-specific response to a variety of injuries.

==Genetics==
Mutations in the [[ACADM|''ACADM'' gene]] lead to inadequate levels of the medium-chain acyl-coenzyme A dehydrogenase enzyme. This condition is inherited in an [[recessive gene|autosomal recessive]] pattern, which means two copies of the faulty gene in each cell are required for the condition to be manifested; if only one copy is faulty then the individual is a [[Asymptomatic carrier|carrier]] and does not have symptoms of the disease.

==See also==
*[[List of fatty acid metabolism disorders]]

==External links==
* {{NLM|mediumchainacylcoenzymeadehydrogenasedeficiency}}
* [http://www.cdc.gov/genomics/hugenet/reviews/mcad.htm CDC]
* [http://www.newbornscreening.info/Parents/fattyaciddisorders/MCADD.html newbornscreening.info]
* [http://gladwinmedical.blogspot.com/2005/08/medium-chain-acyl-coa-dehydrogenase.html Gladwin Medical Blog]
* {{GPnotebook|422903871}}



[[Category:Inborn errors of metabolism]]
[[Category:Genetic disorders]]

[[nl:Medium Chain Acyl co-enzym-A Dehydrogenase deficiëntie]]
[[de:Medium-Chain Acyl-Coenzym A Dehydrogenase Mangel]]

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