Orphan diseases

Rare Diseases Day

Ania Varezhkova, Atlas

February 29 is rare, so the International Day of Rare Diseases is celebrated on this day (in non–leap years - February 28). Today Atlas will tell you what these diseases are and what can be done to make them even more rare.

What diseases are considered rare

Rare (they are also called orphan) are diseases that occur with a frequency of 1 case per 1500-2500 people. The exact figures depend on the country and are indicated in state acts. In Russia, rare diseases include diseases with a frequency of occurrence of 1 case per 10,000 people.

In total, about 7 thousand rare diseases are known. And although each one is rare individually, there are about 400 million people suffering from rare diseases in the world.

What are these diseases

80% of orphan diseases are genetic, and the remaining 20% can be caused by infections and external factors. Examples of genetic diseases: phenylketonuria, cystic fibrosis, spinal muscular atrophy (SMA), epidermolysis bullosa (butterfly syndrome), osteogenesis imperfecta (crystal man disease), Marfan syndrome, albinism and others.

Non-hereditary rare diseases include mainly ancient infections: bubonic plague, typhus, cholera. There is a treatment for many of them, and they are less dangerous, so we will only talk about genetic diseases later.

How rare hereditary diseases are transmitted

For all genetic traits, not only for diseases, there are two variants of inheritance: dominant and recessive. If the sign is dominant, it will manifest itself in any case: regardless of what is "written" in the second copy of the gene.

If the trait is recessive, it will manifest itself only if the mutations coincide in both genes inherited from the father and mother. This happens if both parents are carriers of the same genetic disease. You may not know about the positive status of the carrier: if the mutation is only in one copy of the gene, then the working second copy ensures the normal operation of the protein.

Depending on the variant of inheritance and on which chromosome the damaged gene is located, the maximum risk of transmitting a hereditary disease can be 100%, 50%, 25% and 0%.

For genes located on sex chromosomes X and Y, this probability may vary depending on the sex of the child. For example, boys have only one X chromosome, and they get it from their mother. If a woman is a carrier of an X-linked recessive disease, for example, hemophilia, then for her daughter the probability of inheriting the disease will be zero (if the father is healthy), and for her son the risk of the disease will be 50%. The woman herself may not be aware of her status.

A famous example: Empress Alexandra Feodorovna, the wife of Emperor Nicholas II. She gave birth to four healthy daughters, but her only son Alexey inherited an X chromosome with a mutation and suffered from hemophilia.

Most of the rare hereditary diseases are inherited according to the recessive variant.

How to cure hereditary diseases

So far, no radical treatment of hereditary diseases has been found – such as to correct an error in the work of a defective gene once and for all.

Nevertheless, for many diseases there is a symptomatic treatment, thanks to which the manifestations of the disease can be minimized. With homocystinuria, a disease in which, due to a lack of one enzyme, the level of homocysteine increases and the walls of blood vessels are damaged, vitamin B12 is prescribed. You will have to take it all your life, but it will be the only reminder of the disease.

Unfortunately, there are diseases for which there is no cure today. With spinal muscular atrophy, children are born outwardly healthy, but after a few months or years their muscles atrophy, and they gradually lose the ability to move, sit, swallow, breathe. They are transferred to power through a probe (a tube in the throat) and connected to a ventilator. At the same time, children continue to develop (intelligence does not suffer from the disease) and can live for several decades with the help of auxiliary means.

Since many hereditary diseases are monogenic, that is, caused by a single point mutation, great hopes in the treatment of these diseases are pinned on the method of genetic editing CRISPR–Cas9. But the actual application of this technology in clinical practice is still far away.

What else can be done

• Spread information about diseases
  Every year more and more countries and people join the movement to combat rare diseases. Thanks to coordinated efforts, significant progress has been achieved in the diagnosis and treatment of diseases. You can contribute to this by sharing this article or a link to the website of the Union of Patients and Patient Organizations for Rare Diseases.

• Support scientific research
  It is more difficult for large research institutes to get funding for research on rare diseases: they are expensive, and the results will be useful only to a small number of people. You can make a charitable transfer on the Rare Disease Day website.

• Support children's families, 
  who have faced genetic diseases
  In Russia, such families are helped The Vera Hospice Foundation and the Lighthouse House Children's Hospice.

• Find out your status and try to reduce the risk of diseases for your children.

How to determine your carrier status

For diseases that are inherited by the dominant variant, there is no concept of "carrier". If a patient has at least one copy of a gene with a mutation, he will be sick and will know about his illness.

For diseases with a recessive variant of inheritance, the carrier is a person who has one copy of the gene with mutations. Such a person is usually healthy and does not know about his status. But if he meets another person with the same mutation, or if the mutation is in the sex chromosomes, then such a person has a risk of transmitting the disease to his children.

Today, the only way to determine your carrier status is genetic testing. In order to immediately check for many diseases, rather than taking tests one at a time, screening genetic tests are recommended. The Atlas genetic test examines the carrier status of 283 hereditary diseases.

It is recommended to undergo an examination before pregnancy. It is better to take the test to both partners and, based on the results, consult a geneticist.

What should I do if it turns out that the partners have the same carrier status and there is a risk of having a sick child? This is a difficult question that is better discussed with a doctor. The decision depends largely on the parents, their religious and ethical views. If the disease is serious, doctors can offer IVF and genetic screening of the embryo, but the decision in any case remains with the parents.

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