What are leukodystrophies?
Leukodystrophies (or LDs) are known as dysmyelinating disorders: they are different from MS or multiple sclerosis. In MS, (which is an example of a demyelinating disorder) the myelin is normal at first but is eventually stripped off the nerve, but in LDs, an abnormality of metabolism causes the turnover (reproduction) of myelin or the structure of the myelin itself to be abnormal.
What types of LDs are there?
There are multiple types of LDs: some of them involve inheritance via the X chromosome (one of the sex chromosomes, Y being the other). Others, conversely, have two recessive copies of chromosomes, one of which they have received from each parent. If there is a normal chromosome present, the disease is not seen: i.e. the person is a carrier of a disease and they show no symptoms, but they may pass the disease on to future generations. The abnormalities are split into two categories: deficiencies and mutations, as the table below demonstrates.
What types of leukodystrophies are there?
There are six key types of leukodystrophies that are known, and they are explained briefly in the table below:
When do these diseases first appear?
Children with these disorders are normal at birth. The effects become clear though during the infancy period and throughout childhood as their development becomes delayed when compared against other children of a similar age group. Generally, the earlier the disease starts, the more severe the symptoms and prognosis end up being.
What are the symptoms of LD?
There are four chief symptoms to watch out for when diagnosing LDs:
- Ataxia: loss of the ability to control the way your body moves
- Deterioration of motor skills
- Hypotonia: otherwise known as low muscle tone
- Spasticity: the body experiences spasms
Where do LDs attack within the brain?
LDs have a tendency to attack the white matter located deep within your brain. Here’s a tip for you help remember the layering structure: look at an orange: the outer peel would be equivalent to the grey matter and the inner flesh would be the equivalent of the white matter In people with LDs the white matter would have a lower volume than normal and the colour would appear translucent and similar to the grey matter of the cortex. The ventricles which hold CSF (cerebrospinal fluid) therefore become bigger due to the volume change and myelin is lost.
How are LDs diagnosed?
They can be diagnosed through either a genetic screen via the PCR (polymerase chain reaction) method or via analysing it through a biochemistry analyser.
What is PCR?
PCR is also known as the polymerase chain reaction, and it involves converting a very small amount of DNA into a large amount which can be analysed with a computer. All kinds of samples are put through this method to extract the DNA, and in the medical profession it can be used for analysing both human DNA and for the identification of infectious agents which cannot be identified via more conventional means. The steps are as follows:
- Denaturation: The sample is heated to 94 degrees C for approximately 1 minute. This is done in order to ‘unzip’ the double helixed DNA into their single strands.
- Annealing: The sample then cools down to 54 degrees C for approximately 45 seconds. This is done in order to attach the forward and reverse primers onto the exposed single strand.
- Extension: The sample is then heated up to 72 degrees C for approximately 2 minutes. This is the ideal temperature for the building of new strands of DNA.