Third diagnosis in one family: Armenian geneticist on rare diseases

February 28, 2023  16:29

Spinal muscular atrophy, especially early infantile, i.e., type 1, is a rare but terrible disease. If treatment is not begun immediately after birth, and is very expensive, the child dies before the age of 2 years. But the disease is usually not diagnosed immediately, and when parents realize that the child has a problem, it is too late.

Spinal muscular atrophy is a hereditary neuromuscular disease caused by the gradual and irreversible dysfunction of the spinal motor neurons, which leads to weakening and then atrophy of the muscles.

With type 1 SMA, a child notices muscle weakness in the first months or even the first weeks of life. "In other words, the child fixes his eyes, he is not mentally retarded, but he has muscle weakness, if earlier he moved his arms and legs, he stops doing that, then there are disorders of swallowing, then respiratory disorders begin, and the child dies. Children whose parents carry a certain genetic mutation have the disease. That is, each of the parents must be a carrier for the child to have two mutations and manifest the disease. If both parents are carriers of the disease, their children have a 25% chance of repeating it and that is a very high probability," said Armenian Geneticist Natella Kostandyan, who is a physician, to Medicine. 

We had agreed to talk about rare diseases in general, but we are now turning to the topic of SMA, because last year the doctor saw two families who had lost two children to this disease. The doctor was struck by the similarity of the cases and the lack of understanding of the parents, or perhaps of the doctors in the community, as to the seriousness of the situation.

In one family with one healthy child, a second child died of SMA. This was several years ago, after which the parents were tested for carriage and warned that in their case, the likelihood of the next child repeating the disease was very high. Therefore, the mother, as soon as she gets pregnant, should undergo prenatal diagnosis. But the family turned to Natella Konstandyan when the third child was 3 months old. He was also diagnosed with the terrible diagnosis of SMA, and the child is currently receiving expensive treatment with the support of a foundation. "But the child began receiving medication when he was already on a ventilator, and at that point the disease is incurable. If the disease had been diagnosed at least immediately after birth, it could have been stopped. True, such treatment is not yet available in Armenia, but we already have positive experience in Russia," she said.

To my question of surprise that if the parents were warned, the doctor conducting the pregnancy was aware of why everything happened so, Natella Kostandyan answers that she does not know at what point the chain was broken: the parents themselves did not understand how serious, the gynecologist did not understand what it was about, or even mom just did not inform her gynecologist ...

About the same situation with the second family who had two children who died of SMA, one at seven months old and one at three months old. 

The second child was diagnosed with SMA by Natella Kostandyan, and after his death, the parents were given a conclusion that the probability of recurrence of the disease was very high, so the mother should come for examination and a prenatal test as soon as she became pregnant. The woman came, of course, but... in the 35th week of pregnancy, when it just didn't make sense to examine the fetus anymore. To the doctor's perplexed response, the woman said: "God is great."

The woman had recently given birth, the baby was tested, and while we were talking to the doctor, the diagnosis came in - type 1 SMA - the third diagnosis in one family.

In the case of this child, says Natella Kostandyan, at least it would be possible to try to start treatment right away and save him.  "We will start working with the foundations to start treatment quickly and give the child a chance. This woman is having her third C-section, if this baby doesn't survive as well, she won't be able to give birth again," she says.

The prenatal test for SMA, the geneticist says, allows the fetus to be examined at 11-12 weeks of pregnancy, another 3-4 weeks for the diagnosis itself, and if the result is positive, the pregnancy can be terminated. The ideal variant for parents carrying this mutation is IVF treatment, when an embryo is tested for SMA, and only the healthy embryo is implanted.

Once again, the conversation turns smoothly to the general concept of rare diseases. By global standards, rare are those diseases that are individually rare. Each country has its own figure: on average, it is less than one case per 2,000 population; there are countries that count less than 1 case per 10,000 population. But if you add up all the rare diseases, there are a lot of them. Even during one conference, there was this motto: "Rare but not alone."

"Why do rare diseases require special attention. Because even if they are curable, pharmaceutical companies do not invest in their treatment, it is not profitable. In all countries, certain funds are involved, or their treatment is taken over by the state. Rare diseases are treated with the so-called orphan (orphan) drugs, which are not used very often and are therefore very expensive," says the doctor.

Rare diseases include in addition to SMA Pompe disease, many metabolic diseases - mucopolysaccharidosis, also phenylketonuria, but it no longer refers to orphan diseases, because there is a developed affordable treatment for it. "There are diseases that we haven't even seen in Armenia. We have a lot of diagnoses that remain with a blank column: we simply do not identify them because there are no available diagnostic methods or patients die before they get to a specialist who can make a correct diagnosis," she explains, adding that the list of rare diseases is different in different regions of the world. In Russia, for example, the periodic disease is considered rare, while in Armenia one in four is a carrier of the mutation.

Every year, February 28 (or February 29 in leap years) marks the International Rare Disease Day. This day is established and held by the European Organization for Rare Diseases (EURORDIS) and more than 65 partners from national patient associations since 2008.

According to studies (2019), rare diseases affect 3.5% to 5.9% of the world population, equivalent to 300 million people worldwide (4% of an estimated world population of 7.5 billion).

In the EU, as many as 36 million people live with rare diseases. There are an estimated 25 to 30 million such people in the United States.

To date, more than 6,000 different rare diseases have been identified. 72% of rare diseases are genetic, while others are the result of infections, allergies, and environmental factors. 70% of rare genetic diseases begin in childhood.

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