Monday , May 17 2021

Prevalence rate 1 in 1 million people, familial amyloid neuropathy-Maeil Economy



Genetic factor, but not 100% affected
Professor Oh Ji-young of Konkuk University Hospital “Continue treatment because it could not be cured”

Familial amyloid neuropathy is an extremely rare disease, with an estimated prevalence of 1 in 1 million people worldwide.

This disease is a genetic disease that occurs when amyloid accumulates in peripheral nerves, as can be seen from the name of the disease. As amyloid accumulates in the peripheral nerves, the corresponding part of the body loses its normal function. Pain and tingling begin with a decrease in limb and foot sensation, and phenomena such as muscle atrophy and muscle strength decrease.

Familial amyloid neuropathy has been found in Sweden and Japan since the first patient was reported in Portugal in 1952 and is still occurring. In the past, the incidence rate was high in certain regions, but as disease awareness has increased and diagnostic technology has evolved, it is reported almost all over the world.

Familial amyloid neuropathy results from a mutation in a gene that synthesizes a protein called transthyretin. Transtyretin plays a role in the transport of hormones in our body, and it is produced by the liver. However, when the gene that synthesizes this protein mutates, abnormal transthyretin is produced. The abnormal protein is unstable and breaks into small pieces, and the broken pieces become entangled, forming an amyloid like a nylon thread.

With the help of Professor Ji-Young Oh from the Neurology Department of Konkuk University Hospital, we will discuss familial amyloid neuropathy through Questions and Answers.

-This disease is caused by genetic factors

▷ When amyloid travels through blood vessels and accumulates in peripheral nerves and various organs, symptoms begin to appear. Because it is inherited as autosomal dominant, if one parent is a patient, the probability that a child will be born with a mutated gene is 50%. However, even if they are born with a mutated gene, 100% of them do not develop the disease. It is not yet known which factors cause the symptoms and which prevent them. This means that, although there is a genetic background, heredity does not affect it 100%. It is known to be difficult to diagnose unlike general genetic diseases because it is a complex disease in which protein mutations have occurred but may have no symptoms.

Genetic diseases usually appear from birth or from childhood, while familial amyloid neuropathy varies depending on the type of genetic mutation, but usually begins in the 40s to 50s. Therefore, if the family history is not clear, both patients and medical staff can hardly suspect a genetic disease. This is also the reason for delaying the diagnosis.

-Can it be diagnosed only with symptoms?

▷ Symptoms of familial amyloid neuropathy occur as mentioned above, such as numbness of the hands and feet, dizziness in a standing position, diarrhea or constipation of unknown cause, weight loss, and carpal tunnel syndrome. Just because one of these symptoms occurs, it is too early to suspect that it is familial amyloid neuropathy. This is because other peripheral neurological disorders also have these symptoms.

Numbness and pain at the tips of the fingertips, loss of objects from the hand due to dullness, symptoms of ignorance of the wound on the feet and palpitations, dizziness when getting up, repeated symptoms of constipation and diarrhea, difficulty urinating, dry mouth, glare, etc. are common symptoms in the peripheral neuropathy caused by several causes, so it is not possible to diagnose whether familial amyloid neuropathy is simply a symptom. An accurate diagnosis is essential. However, if you have heart-related abnormalities like arrhythmia or heart thickening, chances are high, and especially if there is someone in your family who has been diagnosed with the disease, it is better to visit a hospital and get a diagnosis from a neurologist. Prior to that, even if diagnosed, families were reluctant to be tested because there was no method of treatment, but as treatment has become possible recently, even if there are no symptoms, it is recommended to check for a mutated gene by genetic testing when adulthood.

If you turn out to be a carrier, you need regular counseling and medical checkups so you don’t miss the proper place of treatment.

-How are you treated and how can it be cured?

He continues to be treated with medication and cannot be treated with surgery. There is also a method of liver transplantation, but it is not very helpful in the case of genetic mutations that occur in Korea.

A typical drug is ‘Vindakel’, an oral drug. This helps the mutant transthyretin no longer transform into amyloid by stable retention of the mutant transthyretin not to break down. In the past, the patient’s burden was high, but in Korea it has been possible to apply insurance since last year, reducing the burden on the patient.

In addition to Vindakel, there is a drug called ‘Onpartro’, a product for intravenous gene therapy. In Korea, it is not yet certified by the Ministry of Food and Drug Administration, but if an intravenous injection of Onpartra is given once every three weeks, the drug is absorbed in the liver, binds to the transthyretin gene, and gene cutting. This prevents transthyretin from being produced at all. I am currently treating 5 patients with this method through international clinical trials and it is a very effective method of treatment. However, since the cost is an astronomical price, you will need a lot of time and effort until it is used in Korea.

Once deposited, amyloid is not easily removed, is permanent, and gradually progresses, making it difficult to cure. However, early detection and treatment with drugs should not be discouraged as they can prevent amyloid deposits in various organs and nerves as much as possible.

I feel the limitations of doctors as I observe patients suffering from extremely rare diseases, as well as their families. However, it is also helpful because we work hard to recognize the benefits of treatment drugs and face difficulties together. Fortunately, despite the extremely rare disease, therapeutic drugs using the latest techniques are continuously being developed. Even if the neuropathy is already advanced, if you can walk, you can start medication. Even if you have asymptomatic mutated genes, you can slow the progression of symptoms as much as possible if you start regular check-ups with medication at the appropriate treatment site. Because it attacks invasive systemic organs, there are so many severe symptoms, and a family that has to watch it from the sidelines has no choice but to feel helpless and fear that one day I will be like that. I will do my best so that patients and their families are not alone.

※ Help = Professor Oh Ji-young, Department of Neurology, Konkuk University Hospital.

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