Russian doctors discussed the problem of identifying hereditary diseases in newborns

Since the beginning of last year, neonatal screening for genetic diseases in infants has been expanded from 5 to 36 nosologies. As a result, over the course of a year, it was possible to diagnose more than 650 rare diseases in the early stages – when there are no symptoms yet, but treatment can already begin.

However, doctors are faced with an unexpected problem: some mothers in maternity hospitals refuse free testing of their children. These cases are not widespread, but they are very alarming. Experts from the leading Russian institution for working with orphan diseases, the Federal State Budgetary Institution “Medical Genetic Research Center named after Academician N.P. Bochkov,” spoke about this.

An expanded neonatal screening program for 36 hereditary diseases and groups of hereditary diseases started in Russia in January 2023. Since then, more than 1 million 230 thousand newborns have been examined, of which more than 22 thousand infants were at risk for the development of hereditary diseases. To date, 656 children have been diagnosed with rare genetic diseases. The largest group (363 cases) consisted of hereditary metabolic diseases (frequency in the Russian Federation – 1 case per 3388 newborns). In addition, 179 primary immunodeficiencies (1:6872) and 114 cases of spinal muscular atrophy (1:10,789) were diagnosed. On average, hereditary diseases are detected through screening in one out of 1,875 children born. Experts say that there will be more diagnoses – not all the final stages of complex molecular genetic research have been completed.

Most often, orphan diseases in 2023 were identified in the Republic of North Ossetia-Alania, the Vologda Region and the Republic of Buryatia. Most rarely – in the Primorsky Territory, Moscow and Vladimir regions.

— Today there are 8 regions where screening has not detected a single patient with hereditary diseases. In 6 regions this can be partly explained by low birth rates. But in 2 regions (Ulyanovsk region and the Republic of Ingushetia) the situation requires separate study,” said Sergei Voronin, head physician of the Medical Genetic Research Center named after Academician N.P. Bochkov. “In addition, in a number of territories, the frequency of detection of hereditary diseases turned out to be much lower than expected. Now our specialists, together with specialists from the National Medical Research Center for AGP named after. V.I. Kulakov conducts an on-site audit there.

Experts are surprised by the fact that some parents refused screening in the maternity hospital. “The refusals are isolated, but they impress us very much,” says Sergei Kutsev, chief freelance specialist of the Russian Ministry of Health in medical genetics. – How so? There is a misunderstanding of the importance of screening in society. Sometimes you have to wait several months for a child who is already suspected of having a hereditary genetic disease.”

For example, there is a case where, due to the mother’s refusal to screen, the child could not be diagnosed with spinal muscular atrophy at the preclinical stage: the baby was diagnosed only after symptoms began, several months after birth. Precious time for therapy that would have avoided the onset of symptoms was lost. “Therefore, doctors need to remain vigilant and monitor symptoms in children,” says Olga Shchagina, head of the molecular genetic diagnostics laboratory at the Moscow State Research Center.

It is curious that the frequency of occurrence of SMA, which experts identified during screening, was not at all what was expected. “Pilot projects allowed us to calculate the average incidence rate in Russia of spinal muscular atrophy of 1 per 7700–7900 newborns. But based on the results of the first year of work, the frequency of occurrence turned out to be statistically significantly lower than expected. We also observe a tenfold variation in the frequency of occurrence across regions. For example, SMA was most often detected in 2023 in the Republic of Udmurtia and the Ryazan region. Most rarely – in Moscow, the Republic of Tatarstan and the Stavropol Territory.

Who needs a consultation with a geneticist? “Patients are referred to a geneticist to clarify the diagnosis of a hereditary disease,” says the head of the scientific advisory department of the Medical Genetic Research Center named after Academician N.P. Bochkov, MD. Tatiana Markova. — You should contact a geneticist if a child was born with congenital anomalies of organs, eyes, nervous system, skin, skeleton… Retarded growth, psycho-speech, sexual, motor development, if the diagnosis is not specified and standard treatment methods are ineffective, especially if there are similar symptoms in the family, this is also a reason to visit a geneticist. The manifestations of hereditary diseases are very diverse; they are often disguised as other diseases, which makes their diagnosis difficult. And often patients are seen by different doctors for years, but still don’t know what’s wrong with them until they turn to a geneticist, who can put together a single picture of a hereditary disease from the symptoms.”

Today, specialists have a wide range of molecular genetic studies in their hands, including gene analyses, sequencing of DNA sections and the entire genome, but the results should only be interpreted by a geneticist. Early diagnosis of hereditary diseases is important not only to prevent serious complications, but also to clarify the cause, as well as to prevent repeated cases of the birth of a sick child in the family.

Experts emphasize that neonatal screening is carried out only for those diseases for which early detection allows early treatment to begin. However, there are many orphan diagnoses for which early therapy does not matter: they are treated only when symptoms appear. In this case, it is more effective to carry out selective screening – this is not examining everyone, but only those who are at risk and who are suspected of having one or another rare diagnosis.

The third approach is when neither mass nor selective screening is effective. The patient comes to the doctor with symptoms, and deep phenotyping is carried out in order to make a diagnosis, including ultra-rare ones. Even if there is no treatment for this disease, parents will have the opportunity to prevent the birth of another child with this diagnosis (for example, through pre-implantation diagnostics before IVF, which allows for the selection of a healthy embryo).

As for the so-called preconception screening (testing for carriage of recessive mutations in healthy spouses before conceiving a child), then geneticists do not yet see conditions for its implementation in Russia. “It is unclear which groups to study; It is unclear how ethical this is. Although in some countries such screening has shown effectiveness. But it is possible only where it is possible to terminate a pregnancy at any stage and there are possibilities for pre-implantation diagnostics. But in Russia many issues have not been resolved, especially in terms of ethical and organizational issues,” says Olga Shchagina.

As for the treatment of orphan diseases, geneticists say that there are significantly fewer problems with providing patients with the drugs that are available in the country. However, the problem of providing medications to patients over 18 years of age has still not been solved: upon reaching adulthood, funds stop funding treatment, and it must be provided by regions, which often do not care. And often the successes achieved in treatment simply go down the drain. Doctors are calling for federalization of drug provision for such patients in order to equalize the rights of citizens throughout the country.

Experts also believe that it is necessary to popularize screening – both among the population and among primary care doctors, who are also often simply not aware that such diseases exist. “Hereditary diseases are not so rare; a huge number of the population may face this problem. And many children today can be treated if diseases are detected as early as possible,” says Olga Shchagina.