How to Recognize Hereditary ATTR Amyloidosis Disease?

Hereditary hATTR amyloidosis is a rare, autosomal dominant amyloidosis in which abnormally folded transthyretin variants are formed by various mutations in the TTR gene.

GENETIC

More than 150 different amyloidogenic mutations are known, which manifest in different ways in patients. However, the most common mutation seen in patients is Val30Met (V30M). Then, the other mutations found in patients are Thr60Ala (T60A) and Val122Ile (V122I).

SYMPTOMS OF AMYLOIDOSIS DISEASE (HATTR)

Clinical symptoms of amyloidosis in patients are characterized by organ damage induced by tissue deposition of amyloid, subsequent to transthyretin mutation. These deposits gradually reach the nervous system, the cardiac system (the heart), the kidneys, the eyes, the tendons and / or the ligaments.

If the nervous system is mainly affected, TTR hereditary amyloidosis disease is also called familial amyloid polyneuropathy (FAP), if the cardiac system (heart) is mainly affected, TTR hereditary amyloidosis is called familial amyloid cardiomyopathy (CAF). However, this old symptomatic classification ignores the fact that most TTR mutations are deposited in both nerve tissue and cardiac muscle (heart).

Note that deposits of amyloid substances can have different origins: an abnormal protein, the consequence of prolonged exposure to a normal protein (but a protein produced in too large a quantity) or even the natural aging process.

Also, it is more correct to speak of amyloidosis (in the plural) than of amyloidosis. Indeed, there are different amyloidosis. Amyloidosis is one of the rare diseases. Some amyloidosis is a genetic disease, like the one mentioned in this article, but not all amyloidosis.

Some of the possible symptoms of amyloidosis disease include:

• General symptoms (weight loss, nausea, fatigue, insomnia)
• Peripheral neuropathy with motor weakness of the legs and sensory disturbances
• Autonomic neuropathy with disturbance of intestinal and bladder motor functions, hypertension and sexual dysfunction
• Heart failure (restrictive cardiomyopathy)
• Dyspnea
• Arrhythmia (palpitations, atrial fibrillation)
• Angina pectoris
• Heart damage (syncope or sudden cardiac death)
• Visual disturbances
• Renal dysfunction
• Thyroid gland dysfunction

The appearance of symptoms of amyloidosis varies considerably from one individual to another, at least for unrelated carriers. In addition, hereditary transthyretin amyloidosis disease can begin as early as the age of 20. In addition, the correlation between the mutation and the symptoms of amyloidosis is generally weak. For patients of the same family, however, the course of amyloidosis disease and clinical symptoms of amyloidosis disease are relatively constant.

DEFINE A DIAGNOSIS OF AMYLOIDOSIS (HATTR)

The heritable mutations TTR can be detected at the molecular level by a genetic test. However, due to the relatively late onset of amyloidosis and non-characteristic manifestations of amyloidosis, this method is rarely used directly.

The measures that can lead to a diagnosis of amyloidosis are:

• Family history
• Neurological examination
• Laboratory (Troponin, BNP, NT-proBNP)
• ECG (low voltage despite thickening of the left ventricular wall)
• Imaging (MRT, CT, scintigraphy)
• Biopsy and immunohistochemistry

The average time to diagnose amyloidosis in patients is 4 years. Note that the diagnosis is often late.

TREATMENT OF AMYLOIDOSIS (HATTR)

For a long time, the treatment was purely symptomatic. Although the underlying genetic defect in amyloidosis still cannot be ruled out, treatment options are available to influence the early signs and progression of the disease in patients. There is also a support program for patients.

DRUG THERAPY FOR AMYLOIDOSIS (HATTR)

• Pharmacotherapy is primarily aimed at reducing the formation of amyloid
• NSAID therapy
• The use of TTR stabilizers
• siRNA
• Antisense oligonucleotides (ASO)

In addition, one or more drug treatments are used to relieve the manifestations of amyloidosis.

SURGICAL TREATMENT OF AMYLOIDOSIS (HATTR)

• Liver transplant
• Heart transplant: replacement of the heart damaged by amyloid with a healthy donor organ
• Combined transplantation

As we’ve been saying all along, genetic testing is a crucial part to diagnose this disease. An early diagnosis will ensure effective treatment of this condition and by determining if you’re at risk, you can speed up this process. If you feel you’re in risk of hereditary ATTR amyloidosis, I must suggest to visit hattrfounders-por.com and fill put their risk questionnaire to find the results.