amyloidosis

introduction

a variety of conditions in which amyloid proteins are deposited in tissues.
a protein is described as being amyloid if, due to an alteration in its secondary structure, it takes on a particular aggregated insoluble form similar to the beta-pleated sheet.

the modern classification of amyloid disease tends to use an abbreviation of the protein that makes up the majority of deposits, prefixed with the letter A.
see wikipedia for details

most clinical effects are via parenchymal ischaemia ⇒ atrophy due to blood vessel compression, but also cause impaired function such as in glomeruli, cardiac muscle, tongue, etc;
spleen: sago spleen as confined to Malpighian corpuscles
liver: in space of Disse in liver ⇒ atrophy may cause portal HT, jaundice, liver failure;
kidneys - in glomeruli, arterioles, interstitial tissue b/n tubules ⇒ nephrotic synd, small scarred, type II renal tubular acidosis (RTA)
heart - enlarged, rigid, firm as b/n muscle fibres & in walls small blood vessels
- ⇒ constrictive pericarditis-like effect;, HB, arrhythmias;
GIT ⇒ tongue ⇒ dysphagia, speech probs; obstruction/ulceration/malabsorption/diarrhoea;
lungs ⇒ nodules may obstruct; infiltrative ⇒ haemoptysis, restrictive failure;
other:
- carpal tunnel syndrome
- lumbar stenosis - aching, cramping and tingling in the legs brought on by walking or standing

ATTR amyloidosis can be hereditary, caused by a mutation in the transthyretin (TTR) gene, but it can also occur as people age without a genetic basis
if left untreated, it is likely to be fatal within four to six years
clinically diagnosed hereditary form was said to be affecting between one in 120,000 and one in 830,000 people globally
HOWEVER, at least 62 TTR gene variants (including Val142Ile) seem linked to this and are far more common suggesting much higher prevalence of undiagnosed hereditary disease ¹⁾
- people with these variants had a 2-3x higher risk of heart failure, thickening of the heart muscle, and heart rhythm problems but only 2.8% had been diagnosed (but diagnosis rate doubled when extra-cardiac evidence was present)
- hereditary form is known to be much more common in certain geographic clusters of populations in Portugal, Japan and Sweden, and among individuals with Black African ancestry
- gene variant rates in UK sample of almost 0.5 million people was 1 in 1000, but rates in those with black African ancestry had a rate of 4.3%

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