Genetic research for the ACADM mutation
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.
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
time consuming. That is why DNA research is difficult, expensive and
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.
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.
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").
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
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.
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
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 >