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Friedreich's Ataxia

Friedreich's ataxia is a multi-system disorder with onset in the first decade. It is autosomal recessive disorder. What we have learned more recently is that, in people who are homozygous and have both alleles. 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.

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. 

These people also have other problems like optic atrophy, cataracts, degeneration of the cochlea nucleus. 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.

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.

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 - 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 may be seen.

Clinical approach to the child with ataxia. A differential diagnosis, localization and so on. So the term comes from the Greek, atactos, which is out of order. So the true definition of ataxia is "It’s a disturbance of coordination and rhythm and volitional and postural movements." And the neuroanatomic substrates are the cerebellum, the midline structure of the vermis, and the hemispheres and its major inputs. One of the important things in neurology, as you try to localize it, is when you have long and complicated circuits involved, the lesion could be in many parts of that and give you a common sign.