8.2 Wilson's disease
The effects of a protein that is absent, or present but not doing its job, may not be evident for many years. This is called late onset, and is exemplified by Wilson's disease. Many molecules within the body require small amounts of minerals such as iron, magnesium or copper to function properly. There are mechanisms for absorbing these minerals from the diet. However, in excess, these same minerals can be toxic, as is the case with copper. So there are also mechanisms for getting rid of, excreting, these minerals. In Wilson's disease a protein (unhelpfully referred to as ATP7B), crucial for removing copper from the blood prior to excreting it, is absent, and copper accumulates. Provided one copy of the normal allele for ATP7B is present in the genome, copper excretion can occur. However, if both copies of the gene are mutant alleles, copper excretion cannot occur and Wilson's disease results. Wilson's disease is only evident when there are two defective alleles, and is an example therefore of a recessive trait. (A dominant trait is where only one defective allele is sufficient for a disease to be manifest, e.g. Huntington's disease.)
Copper primarily accumulates in the liver, so the initial symptoms are often to do with liver function. However, copper also accumulates in the CNS and may result in difficulty in writing or speech, trembling, an unsteady walk or loss of mental functions. Symptoms may appear at any time but usually appear during the teenage years. Note that late onset refers specifically to the conspicuous effects, the symptoms, of the disease; the key protein is missing throughout life.
If the protein is missing throughout life, why don't the symptoms appear earlier than the mid-teens?
The missing protein does not directly cause the symptoms, it is the accumulation of copper that directly causes the symptoms. Copper accumulates very slowly, so it takes many years for sufficient copper to accumulate to produce the symptoms.
In what way does Wilson's disease illustrate pleiotropy?
Pleiotropy is where a single gene has multiple effects. The single gene which is damaged in Wilson's disease has effects that are manifest in problems with movement and liver function.
Provided Wilson's disease is diagnosed before any serious damage is done to the brain or, to a lesser extent, the liver, the outlook for the patient, the prognosis, is very good. Drugs (e.g. zinc acetate or D-penicillamine) can be taken to remove excess copper from the body; and once the excess copper is removed, so is the problem. This illustrates very nicely an often misunderstood aspect of genetic diseases. To have a particular allele in the cells of your body, or to put that another way, to carry an abnormal gene, does not mean that the disease associated with that allele is inevitable: environmental intervention, drugs in this case, can control the expression of this genetic disease.