Genetic research for the ACADM mutation

Genetic research on DNA of the patient will investigate the genes and can identify the mutations on these genes. It is of course impossible to investigate all 25.000 genes present in a human body. But because in the case of MCAD deficiency we know exactly on which gene the mutation is present (the ACADM gene, see the page on the MCAD mutation), we can focus on only this gene.

We also know that different mutations on a gene can cause the same inherited disorder. That is why in each family with a specific inherited disorder the specific mutation has to be tracked. This can be very time consuming. That is why DNA research is difficult, expensive and slow.

In order to track the mutation on the gene, the DNA sequence of that gene has to be determined. As described in the page on DNA and genes, a gene consists of a long chain of the chemical bases A, C, T and G. An example of a (short) piece of such a sequence could be CGGGGATCCTCTAGAGT. This sequence can then be compared to the normal sequence of the gene to track the mutation.

The most classic mutation that causes MCAD deficiency is A985G, where an adenine (A) is replaced by a guanine (G) at position 985.
An other example of a mutation is C1045T where a C is replaced by an T at position 1045.
So different mutations are possible. A patient with MCAD deficiency can have twice the same mutation. Patients with twice the A985G mutation are quite common. This is called homozygous.

A patient can also have 2 different mutations, for example A985G on one gene and C1045T on the other one. This is called compound heterozygous.

Some mutations cause a severe form of MCAD deficiency where the enzymatic activity is strongly reduced.
Other mutations seems to be milder and cause a less strongly reduced enzymatic activity. This would then be mild MCAD deficiency.

At this moment no clear connection can be made between the genetic mutation ("genotype") and the degree in which the MCAD deficiency presents itself in the patient ("phenotype").
It is for example possible that 2 patients (even siblings!) are both homozygous for A985G, but still react differently in times of metabolic stress. One of them will only get in trouble after 36 hours of fasting, while the other could already show symptoms after only 12 hours of fasting.

It is suspected that other factors (other than the mutation on the gene) define the seriousness of the MCAD defiency. But further research is required.

So it is important to know that not only the gene mutation causes the seriousness of the MCAD deficiency, and we can't decide that a specific mutation is mild in a patient because it was proven mild in an other patient.
Individual testing and monitoring of each patient is necessary before we can come to such a conclusion.

Patients who were not yet diagnosed, will sooner or later present themselves in the hospital with a metabolic crisis.
Read further about how the diagnosis can be suspected from such a crisis >

The information on this website is a summary of information that is publicly available on other websites as well as information from books for sale on the internet and in public book stores.
The content of this website is not validated by doctors, scientists or geneticists.

This page was last modified on 28 February 2011