ATTR-CM
I’ve been seeing commercials for a newly approved treatment for ATTR-CM or Transthyretin Amyloidosis, a condition most of us have never heard of before. This is a progressive genetic condition that can damage the heart and other organs when the gene for transthyretin has a mutation that causes the protein it produces to make destructive aggregates. If you look up this condition, you will see that the gene for transthyretin (TTR) is on chromosome 18q. But that does not mean that someone with a deletion or duplication of this gene will have ATTR-CM.
The TTR gene is active in the liver to make the transthyretin protein. The transthyretin protein acts in the bloodstream to carry thyroid hormone and vitamin A to different parts of the body. Although the gene for transthyretin is a linear set of instructions, the protein it codes for is folded into a very specific three-dimensional shape. Just as a recipe for a cake is a linear set of letters and words, it codes for a three-dimensional object, a cake. Almost any typo in the recipe for the cake is likely to make a less than perfect cake. A cake is very unforgiving of changes in the recipe, more so than a recipe for a pasta salad. This is the case with transthyretin. It is more like a cake than a pasta salad. Almost any small change in the genetic code (a mutation) can cause the protein to aggregate and over time those aggregates damage organs. If this mutation is in just one of the two copies of the TTR gene, it will cause the disease.
There is no evidence to date that suggests that someone with, for example, just one or three copies of the normal gene is at risk for ATTR-CM. Too much or too little normal transthyretin is not a problem. The only time there is a problem that causes the transthyretin to make damaging clumps is when one of the copies of the gene has a mutation. Although the gene for this condition is on chromosome 18q, it is not one of the genes we must worry about and is not the focus of our research.
