Transthyretin Amyloidosis are mutated forms of Amyloid fibrils  that affect the heart, the veins, oxygen flow, blood flow, kidneys, brain, liver, pancreas, and can affect life itself. The accumulation of amyloid deposits disturb normal functioning of organs. Some form life threatening diseases. They can cause abnormal heart rhythms, fatigue, shortness of breath, fainting, dizzy when standing, tingling in fingers and toes, swelling of feet, foamy urine, excess protein, easy bruising and enlarged tongue, and marks or bumps on your skin or a rash. Amyloidosis can have a huge effect on your life on your multiple organs. Biopsies have found insoluble, elongated, sticky fibrils in veins so thick they could not get a tool into the vein to get it ready for burial, when trying to remove the blood. You usually have about 13 months to live after these have been found, and some 5 % of persons have lived up to ten years.

There is a presence of shedding in tetramers which means  a molecule (as an enzyme or a polymer that consists of subunits as peptide chains or condensed monomers), break into little pieces, via shedding. Monomers can bind with other monomers to form large molecules. A tetrameric protein with a quaternary structure of four subunits is tetrameric. Homotetramers have four identical subunits such as (glutathione, 5 transferase), and heterotetramers are complexes of different subunits.

Are antibodies tetramers? Antibodies (synonym immunoglobulins) are tetrameric protein molecules composed of two identical heavy chains (H chains) and two identical light chains (L chains) that have the ability to bind to antigens.

If there is the presence of  TTR (a tetrameric transport protein)  the rate limiting step, then this gene provides instructions for making a protein called transthyretin. This protein is found in cells that circulate vitamin A, in your blood, and a thyroid hormone called thryoxine. Four transthyretin proteins must bind together to form a 4 protein unit tetramer, and that results in destabilizing tetramers, and leading to dissociation into monomers, and these monomers misfold and aggregate into insoluble amyloid fibrils. The TTR gene causes transthyretin Amyloidosis.

The most common variant found in people with transthyretin amyloidosis replaces the (amino acid valine with amino acid methionine at position 50 in the transthyretin protein). TTR variants that cause transthyretin amyloidosis alter the structure of transthyretin impairing the ability to form tetramers. As a result the tetramers break down into individual transthyretin called fibrils. The fibrils clump together and form amyloid deposits in certain tissues leading to signs and symptoms of transthyretin amyloidosis. This can be found in kidneys, heart, lungs, in blood vessels, or liver, in the CNS, Peripheral nerve, Autonomic Nervous system, choroid plexus, Spinal chord roots, Spinal ganglia on autopsies, and Amyloid nodules can indent and compress myelinated fibres and are found in epineurium, perineurium the tissue that surrounds axons found through microscopy, and the GI tract, also in joints and skin. Disruption is also found in blood nerve barriers found in electron microscopy.

AL Amyloidosis , which 2.5 out of every 100,000 people are found with underlying plasma cells dyscrasia that produces immunoglobulin light chains that form amyloid fibrils, and deposits through out the body.

Those with Amyloidosis are 17 to 35% of people with AL Amyloidosis, and Autonomic Neuropathy 65% of patients. It can cause mechanical compression, and has potentially toxic effects. Amyloid deposits are in a patchy fashion and lead to blood vessel shedding. There are symptoms of stickiness that develop in intrinsic amino acids sequences of FLC, and they begin elongation processes depending on stickiness, plus symptoms can occur at different FLC bone marrow cell level. There is evidence of plasma cells dyscrasia.

This is a common “Transthyretin Familial Amyloid Polyneuropathy.” Today the biophysical information of this disorder has lead to a therapeutic strategy termed “kinetic stabilization.” Tafimidis or Vindequel is currently the first and only medication approved to treat TTR-FAP.

 

Carolyn d Hogarth Canada

Disclaimers for research on all genetics being the same for brown skinned people vs white, well no one is all white. Or research being clumped into groups, or not being hybrids is ridiculous. But to look at the symptoms, and not how these diseases have been caused, is beyond belief. Covid 19 a huge cause of these presenting forms of disease. Especially to do with immune systems of the individual, and our hybrid familial genomes. Please do your own research with your doctor, or care giver. The reason I do this is it has been a passion of mine for many years. CDH