What Causes hATTR Amyloidosis?

1. What Causes hATTR Amyloidosis? Hereditary transthyretin amyloidosis (hATTR) is a rare, rapidly progressing, life-threatening disease that is inherited as an autosomal dominant trait. There are several mutations in the transthyretin gene. The modified transthyretin tends to misfold with the formation of amyloid fibrils, which are deposited in numerous organs, which explains the heterogeneous symptoms. The nervous system and heart are most commonly affected by this disease. As a result, patients suffering from hATTR amyloidosis are highly susceptible to polyneuropathy and restrictive cardiomyopathy with a risk of heart failure. hATTR amyloidosis is a serious condition. It is a rare disease and one which is very difficult to diagnose. Misdiagnosis is very common and it can take patients several years from symptom onset to get the right diagnosis and start treatment. However, on the bright side, early detection can significantly go a long way in effective treatment against this condition. But what is the cause behind this rare disease? Causes of hATTR Amyloidosis hATTR amyloidosis is caused by a mutation in the TTR gene. hATTR amyloidosis is a hereditary, autosomal dominant disease, which means that a person needs to have only one copy of the mutant gene to manifest the disease and thus can be inherited from one of the parents. The mutation causes the TTR protein to reproduce abnormally and accumulate as amyloid fibers in various organs. hATTR amyloidosis is associated with more than 120 different known mutations of the TTR gene. The most frequent mutation associated with polyneuropathy is V30M, which is responsible for approximately 50% of mutations presented predominantly with polyneuropathy.

2. ●TTR is a protein that exists naturally in the body. It is produced mainly in the liver and helps to transport substances such as vitamin A. ●Genetic mutations can lead to changes in the TTR protein that cause it to unfold into an abnormal shape. ●The change in shape causes the protein to clump and accumulate in the nervous (nerves), cardiac (heart) and gastrointestinal (digestive) systems. hATTR Amyloidosis manifests itself in the form of a wide variety of symptoms. Let’s have a look at some of the most common ones. Symptoms of hATTR Amyloidosis The degree and intensity of the symptoms of hATTR amyloidosis and its onset vary from person to person, depending on the degree to which the organ's function is compromised. The most frequently reported sensory and motor symptoms are: ●Neuropathic pain ●Sensory change (i.e., change to sensitivity to pain and temperature) ●Numbness and tingling ●Muscle weakness ●Imbalance ●Difficulty walking

3. The autonomic symptoms frequently reported are: ●Nausea and vomiting ●Changes in gastrointestinal motility (i.e., diarrhea, constipation, gastroparesis, early satiety) ●Orthostatic hypotension (i.e. dizziness and fainting after standing up) ●Bladder dysfunction ●Erectile Dysfunction Cardiac symptoms frequently reported are: ●Shortness of breath ●Edema ●Palpitations and arrhythmias Other frequently reported symptoms: ●Carpal tunnel syndrome ●Widespread fatigue ●Unintentional weight loss ●Eye changes (i.e., blurred vision, blindness) Diagnosis Patients with hATTR amyloidosis need an early and accurate diagnosis due to the natural rapid progression of the disease. As hATTR amyloidosis is often misdiagnosed due to its great diversity of symptoms, which can overlap with many other common diseases, many specialists are often consulted before diagnosis.

4. As the etiology of hATTR amyloidosis is different from other diseases with polyneuropathy and cardiomyopathy, a wrong diagnosis can result in an ineffective and possibly harmful treatment. hATTR amyloidosis should be considered in patients with progressive neuropathy or cardiomyopathy with multisystem involvement, especially in those with a family history of amyloidosis. hATTR amyloidosis is diagnosed in several ways, blood tests and biopsies are often used to confirm the presence of the amyloid protein TTR. Genetic testing can also be used to identify the specific TTR mutation. Other diagnostic tests for hATTR amyloidosis with polyneuropathy may include studies of nerve conduction and/or renal function tests. Echocardiograms, cardiac magnetic resonance imaging (MRI) and bone scintigraphy can also be used to help diagnose patients who have predominant symptoms of cardiomyopathy. Get Yourself Diagnosed If you have a family history of hATTR amyloidosis and your body is starting to show some initial signs of its onset, it is strongly advised to get yourself diagnosed as early as possible. Early detection can help significantly in treating it and stopping it from becoming a life-threatening condition. There are several, clinically tested, treatments available for hATTR amyloidosis that are very effective in treating it. Take a quick risk survey and ask your doctor for more information about genetic testing for hATTR amyloidosis to get started.