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Ataxia Telangiectasia

Ataxia telangiectasia is an inexorably progressive disease. It is autosomal recessive ataxia telangiectasia, telangectasia. The gene has been cloned. We know now that the defect here is in DNA repair and the onset of the disease is around 1-3 years. There are telangiectasias that are easiest to see in the conjunctiva and in the pinna of skin. They present with dysarthria, ataxia and a very distinctive early finding is oculomotor apraxia. And you are saying, "What is that?" It simply means they cannot initiate saccades very 

When you do the exam on an average patient, if you make them fix their eyes on your eyes and then say, "Look at my eyes, look at my finger" you can go back and forth pretty well. We talked about how you can see dysmetria of saccades. But in this condition itís not dysmetria that would be striking. It will be what we call head-thrusting. They just canít move their eyes so fast so their whole head 

 Thatís classic oculomotor apraxia. They could have lymphoid hypoplasia. So if you see an ataxic kid who has no tonsils and some of the common laboratories that they have are IgA deficient, so if you do QIgís IgA may be deficient. They also have elevated serum alpha fetoprotein. Hereís an example of some conjunctival telangiectasias. You may also catch them in the ear because you are not going to see it in the rest of the skin very easily.

Friedreich ataxia, an important disease. Also called spinal cerebellar degeneration. And this is a multi-system disorder with first decade onset. It is autosomal recessive. What we have learned more recently is that, in people who are homozygous and have both alleles, there is a triplet repeat expansion. I alluded to this earlier when we talked about congenital myotonic dystrophy. We have a variety of diseases now that belong to this family. You will probably hear about this more from the genetics people but the idea is that in the decade we are learning that a variety of bad diseases, particularly those with anticipation for successive generations get worse, occur from triplet repeats. Where a sequence of three nucleic acids, like CTG - normal people have, for example, 15 repeats in a particular site. The next generation goes to 40 and they are not so well. The following generation has 200 repeats and they get 

We learned about this first in hunting for the gene for Huntingtonís disease. Now we find that itís a classic paradigm of disease. So itís involved in several of them, including Friedreich ataxia. So we call them "unstable triplet repeats". Meaning, every body has there repeats but they get expanded with successive generations. Friedreichís is truly multi-system. It affects peripheral nerves and the spinal cord. So we talked this morning about spinal muscular atrophy, and these people have an element of that. They also have other problems like optic atrophy, cataracts, degeneration of the cochlea nucleus. They can develop

We send a little blood to the lab and they can analyze it for triplet repeat expansion and tell you within three days this rather horrible diagnosis. You will notice that as much as the list is long, the disease does not affect the cerebral cortex. So these people are completely normal intellectually. They tend to experience fully their annual deterioration. Eventually they lose communications skills due to significant dyssynergia of phonation and itís quite a heartbreaking disease.

Bassen-Kornzweig syndrome is another interesting disease that can cause ataxia -and this again is kind of related to something Marvin Ament told you speaking of vitamin deficiencies - itís called Bassen-Kornzweig syndrome. Most of us just call it a-beta lipo-proteinemia, or more commonly, neuro-acanthocytosis. So what it is Ö the easiest way to diagnose this particular condition, is to order a peripheral smear. An abnormal acanthal erythrocytes may be seen. There is also degeneration of the posterior columns. I was surprised to hear that in your gastroenterology lecture. But thatís because there is a problem with fat-soluble vitamin absorption. There is retinitis pigmentosa, mental retardation has a lot to do with malabsorption of fats with