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Abetalipoproteinemia (Bassen Kornzweig Syndrome)

Abetalipoproteinemia (Bassen Kornzweig Syndrome) is another interesting disease that can cause ataxia  - and this again is kind of related to vitamin deficiencies - it’s called Bassen-Kornzweig syndrome. Most of us just call it a-beta lipo-proteinemia, or more commonly, neuro-acanthocytosis. So what it is … the easiest way to diagnose this particular condition, is to order a peripheral smear. An abnormal acanthal erythrocytes.

There is also degeneration of the posterior columns. I was surprised to hear that in your gastroenterology lecture. But that’s 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 beta lipoprotein problem. So in some people, early treatment with vitamin E.

Friedreich ataxia 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 very sick. We learned about this first in hunting for the gene for Huntington’s disease. Now we find that it’s a classic paradigm of disease. So it’s 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. Friedreich’s 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.

They can develop cardiomyopathy, 40% of them may develop diabetes and they usually have skeletal problems that include scoliosis and pes cavus. Very early in their course you may not be able to tell. You are looking at a kid that is 6 or 7-years-old with a little bit of ataxia. He doesn’t walk right and you look at the feet and he has pes cavus and you are not sure the vibratory strength is all that normal. The reflexes are diminished. What would you do? Well, ten years ago you would say, "Well, we really have to see Johnny back again. This could be Charcot-Marie-Tooth or it could be something worse." Well, that something worse could be Friedreich’s. And today we don’t do that. 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.

Ataxia telangiectasia is another one that is an inexorably progressive disease. Again, it is autosomal recessive. 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. Again, 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 readily. So as I told you earlier, 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 it’s not dysmetria that would be striking.