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.