Réseau Amylose Site Patient
Faire un don
01 49 81 22 53

Different types of amyloidosis

Les types d'amylose

AL Amyloidosis
AL Amyloidosis is the most well-known form of amyloidosis, affecting a slightly higher number of men than women. It most often affects those aged 60 to 80 but can also affect patients who are much younger. It destabilises the immune system meaning that the ‘plasmocytes’ (a type of white blood cell) start to produce an excess of antibodies known as ‘light chains’. These antibodies misfold and form amyloid fibrils which accumulate in the bloodstream and deposit in different systems and organs. This can cause many different problems and symptoms, which is why patients can have a range of complications. AL Amyloidosis can affect the heart, kidneys, liver, spleen, nerves, bowels, skin, tongue and blood vessels. Symptoms may include:
  • Weight loss, fatigue, breathlessness
  • Diarrhoea and/or constipation (Dysautonomia)
  • Loss of balance when standing up (orthostatic hypotension)
  • Sudden appearance of red spots around the eyes (periorbita bruising) or on the body (purpura)
  • Enlargement of the tongue, changes to the voice, deformed nails, etc.
  • Tingling in the hands, mainly occurring during the night (Carpal Tunnel Syndrome)
Link : étude des immunoglobulines
Hereditary transthyretin amyloidosis
Hereditary TTR Amyloidosis is a hereditary autosomal dominant disease. The amyloid deposits in this type of amyloidosis are made up of a protein produced by the liver, called transthyretin. It was first documented by Dr Corino Andrade in 1952 in Portugal, where families carried the same mutation of the transthyretin gene Val30Met. In these families, the illness first appeared at age 30, with most cases having a similar family history, making diagnosis relatively easy. Two other outbreaks of the same mutation have been documented in Japan and Sweden.
More recently, more late-onset forms of the illness have been discovered amongst those aged over 50 with no family history of the illness, making diagnosis more difficult. More than 100 variant forms of the transthyretin gene have been documented. Clinical manifestation differs depending on the age of onset and the type of mutation, which means that diagnosis is often made late. It is estimated that around 400 families are affected by this orphan illness.
Due to the fact that transthyretin is produced by the liver, liver transplantation is the standard treatment for this illness. This can stabilise the neuropathy but only if this procedure is carried out early on.
For around 2 years, new medical treatments have been in development. One of these, Vyndaqel (tafamidis), was authorised to enter the European market in November 2011 as a treatment for early onset transthyretin neuropathy. This treatment is administered orally and is well-tolerated. Results from clinical trials have shown that this treatment slows down the neuropathy’s development. Other drugs and gene therapy techniques are also being developed currently, meaning that there is new hope for treating this illness. Due to the genetic characteristic of this type of amyloidosis, genetic counselling, including family screening, is also available as part of patient care. There are other types of hereditary amyloidosis, for example gelsolin amyloidosis and apolipoprotein AI related amyloidosis, but these are much rarer.
Diagram of transthyretin mutations registered and isolated geographically.
Senile transthyretin Amyloidosis
Senile amyloidosis is called ‘senile’ because it was initially discovered in elderly patients, mainly affecting men (in 98% of cases). The main cause of senile systemic amyloidosis is extracellular intramyocardial deposition of amyloid fibrils composed of ‘wild type’ transthyretin (i.e. it’s not hereditary, the transthyretin gene is not mutated). It is not yet understood where ‘wild type’ transthyretin comes from. It is important to keep track of the number of myocardial amyloids deposited as they cause the myocardium to thicken and in cardiac imaging this can resemble hypertrophy. The main damage caused is cardiological and this is what leads to heart failure, heart block and systemic embolisms. Expert cardiological care is needed for systemic amyloidosis.
It is unknown how common amyloid cardiopathy is amongst the general population, but it is probably under-recognised. This is most likely because heart failure with preserved ejection fraction and myocardial hypertrophy are rarely investigated any further in older patients. It is important that we improve our ability to detect this illness because treatment requires expert cardiological care and the development of specific treatments to prevent transthyretin amyloid deposits. New imaging techniques are also greatly improving diagnostic processes.
AA Amyloidosis
AA Amyloidosis occurs when fibres made of autoaggregated N-terminal fragments of the protein Amyloid A build up in tissue (these fragments are formed by the division of serum amyloid A (SAA)). SAA is an apolipoprotein made in the liver and the concentration of this serum increases considerably with chronic inflammatory conditions (these can be rheumatic, digestive, a hereditary periodic fever syndrome, etc.). The most common complication is renal damage but some patients have also been found to have cardiac amyloidosis.