Enter the "Circle": how not to miss a rare form of rickets in a child
The International Ricket-like Diseases Awareness Day is celebrated on June 23. Everyone knows about rickets, but it has quite a lot of forms, and it is critically important to diagnose the correct one as quickly as possible. This will avoid serious consequences in the future. However, there are still problems with diagnosis: for example, in Russia, the orphan (that is, rare) form of the disease, namely X-linked dominant hypophosphatemic rickets (X-HFR), should be present in about 5-6 thousand people, but only 500 children have it established and genetically confirmed. Izvestia, together with medical specialists and the Rare Case Foundation for Support and Assistance, talk about rare forms of rickets and their treatment.
What are rickets-like diseases?
Svetlana Papizh, head of the Department of Nephrology at the Veltischev Institute of the Russian Ministry of Health, told Izvestia that currently there is no concept of "rickets-like diseases" in the international classification. There are two forms of rickets — hypophosphatemic and hypocalcemic rickets.
The most common is vitamin D-deficient rickets, also known as nutritional rickets, which belongs to the hypocalcemic group. There are also hereditary diseases — these are the five forms of vitamin D-dependent rickets and most hypophosphatemic rickets (GFR). X-linked dominant hypophosphatemic rickets (X-HFR) is most common among HFRS. This disease is considered orphan. With GFR, phosphorus and vitamin D metabolism are disrupted.
Kristina Kulikova, a pediatric endocrinologist at the I.I. Dedov National Research Medical Center of Endocrinology of the Russian Ministry of Health, says that all forms of rickets are characterized by impaired bone mineralization and many other multiple organ complications that occur against the background of dysregulation of calcium-phosphorus metabolism.
"All patients with various forms of rickets are characterized by skeletal deformities, stunted growth, fatigue, pain when walking, dental pathology, and in some cases frequent fractures," she told Izvestia.
Kristina Kulikova explains that doctors, when they see a child with rickety skeletal deformities, often assume that this is due to vitamin D deficiency or nutritional rickets. But it is important to undergo a full range of examinations — to pass biochemical, hormonal tests, undergo X-rays and molecular genetic diagnostics. The most accurate diagnosis will influence the choice of the right treatment.
— For example, nutritional rickets is treated with vitamin D, hypophosphatemic rickets requires the appointment of phosphorus preparations or a pathogenetic drug, — says the specialist. — If the form of rickets is incorrectly established, then the wrong treatment is prescribed, and this leads to a deterioration in the child's condition and the development of severe complications: short stature, decreased motor activity, fractures and, in general, a deterioration in the quality of life of the child and the whole family.
How a correct analysis saved the quality of life
The importance of timely diagnosis is illustrated by the story of Dima, a ward of the Rare Case Foundation from the Volgograd Region. The boy inherited the diagnosis from his mother Irina.
— From the very beginning, I knew that there was a risk of transmission of the disease — doctors talked about a 25% probability, but later I learned that the risk was much higher — almost 50%. The fact is that I have been misdiagnosed with chondrodysplasia since childhood. It was only years later that it became clear that this was not the case," she says.
When the boy was born, Irina carefully began to monitor her son's growth, the shape of his legs, gave him vitamin D, and took him to mandatory medical examinations. There were no abnormalities until the child started walking. That's when the first changes appeared: growth slowed down, and the legs began to deform. It became clear that the disease was manifesting itself. Orthopaedists have been urging people to prepare for surgery since the age of six, using Ilizarov's device, which Irina also wore.
— I understood that a difficult path was waiting for us, but for a long time we could not be accurately diagnosed, — says the boy's mother. — The doctors attributed my diagnosis, someone talked about hip joints, someone - about a congenital deformity. And then I read on one of the medical forums that my diagnosis — chondrodysplasia — is often confused with phosphate diabetes, that is, hypophosphatemic rickets. It was as if something clicked: both Dima and I always had low phosphorus with normal calcium.
At that moment, the family was lucky to get to an attentive endocrinologist, who listened to their suspicions. The first tests turned out to be negative — a mild form of phosphate diabetes was ruled out, but a broad genetic study was also conducted, which showed a breakdown in the PHEX gene. The correct diagnosis is X-linked hypophosphatemic rickets (X-HFR).
— I felt relieved: after several years of uncertainty, tossing and loneliness, we finally knew what we were dealing with. And all is not lost yet: Dima was only seven years old, a lot can be fixed in time," said the boy's mother. — I bought a phosphorus drug, which I read about myself, tested on myself, and started giving it to Dima. During the month, he gained 1.5 cm in height, whereas for the entire previous year — only 1 cm.
Two months later, in April 2021, the family began to be observed at the Dedov National Research Medical Center of Endocrinology. Doctors at the place of residence strictly follow all prescriptions. The family is supported by the Rare Case Foundation, and since July 2022 Dima has been receiving the free drug burosumab from the Krug Dobra state Foundation.
— Phosphorus has not returned to normal yet, but bones are getting stronger, Dima is growing — albeit with a lag, but steadily. And most importantly, there is no longer this endless binding to taking phosphorus six times a day, as was the case with the phosphorus preparation in the form of tablets. Now we just come to the clinic once every two weeks and live a normal active life," says Irina.
Alexander Fominykh, founder of the Rare Case Foundation for Support and Assistance, a father of three children with this disease, notes that thanks to timely and accurate diagnosis and effective therapy, children with hypophosphatemic rickets "not only avoid disability, they flourish," live an active, fulfilling life in which pain and limitations remain only a vague memory.
Irina also says that Dima, despite his illness, is very active: he runs, jumps, plays ball, rides a two-wheeled scooter. He likes to travel to new places, but he does it mostly with his grandmother: mom can't stand for long because of her diagnosis.
If Dima hadn't been diagnosed with the disease in a timely manner, he wouldn't have been able to either.
How many people in Russia with hereditary GFR
Kristina Kulikova notes that hypophosphatemic rickets has several forms of the disease. The most common type is the X-linked dominant GFR. Every 20-60 thousand newborns, one child is born with this disease, which means that in Russia there should be about 5-6 thousand people with this diagnosis.
— However, only 500 children have it established and genetically confirmed, — says the interlocutor of Izvestia. — The rest of the patients with this disease do not have an officially established diagnosis, which is due to the low diagnosis of this pathology.
According to her, so far the awareness of doctors about various forms of rickets is low, although every year more and more specialists learn this information and the age of correct diagnosis is gradually decreasing.
— For diagnosis, it is enough to first perform simple biochemical and hormonal examinations and radiography of tubular bones, which is available in all polyclinics and hospitals in all regions, and for genetic diagnosis there are various programs for which a doctor can send a patient's biomaterial completely free of charge, — added Kristina Kulikova.
Since telemedicine has been developed in the country for a long time, in doubtful cases, local doctors can help the patient consult with leading specialists from federal centers.
Svetlana Papizh notes that regional schools are being held in the regions to familiarize local specialists with the problem in order to improve the diagnosis of GFR. Over the past year, nephrologists from the Veltischev Institute have visited Chelyabinsk, Volgograd, Vladikavkaz, and Kaluga.
However, Yulia Bakhcheeva, chairman of the Rare Case Foundation, notes that late diagnosis is still a serious problem.
— Unfortunately, we know of repeated cases when an adult learns about his diagnosis only after similar symptoms appear in his child, — she told Izvestia.
The Rare Case Foundation has been maintaining a registry of patients with hereditary forms of rickets since 2024. The need for its creation arose due to the lack of a single patient database. There are no exact statistics, but without figures it is impossible to defend the rights of people with hereditary forms of rickets at all levels, the foundation notes.
Do all patients with GFR receive treatment?
Since 2021, the Circle of Good Foundation has been providing children with X-linked dominant hypophosphatemic rickets from one year to 19 years of age with the drug burosumab — it has not yet been registered in the Russian Federation, but it can significantly improve the lives of patients. However, it is very expensive — it is very difficult to provide a child with the drug without the participation of the foundation: the cost of treatment with burosumab for one child costs 15-20 million rubles per year, says Kristina Kulikova.
According to Yulia Bakhcheeva, more than 220 children are currently receiving pathogenetic therapy from the Circle of Goodness Foundation.
But it is more difficult for adult patients: they can be provided with the drug at the expense of the regional budget, but this happens only in isolated cases.
— The Ministries of Health of the regions usually refuse to fulfill their duties to provide the drug, arguing that the drug is not registered in the territory of the Russian Federation, and the issue of financing unregistered drugs is not regulated in the Russian Federation, — said Yulia Bakhcheeva. — In order to protect the rights of an adult patient, it is necessary to contact the prosecutor's office and force the regional authorities through the court to provide the drug prescribed for vital indications.
Recently, for example, we managed to win a court case for one of the foundation's wards and secure the allocation of 16.9 million for a year of treatment for one of the wards. But even after the court decisions come into force, there may be problems.
— For example, a patient in one of the regions has not received the drug for six months. There are various reasons for this, including cases of non—fulfillment of obligations by suppliers who have won the contract," continues Yulia Bakhcheeva. — This devalues the therapy process and resumes health problems.
What symptoms may indicate GFR?
Experts identify the following manifestations of the disease in childhood:
— hypertrophy of the frontal tubercles;
— rickety deformities of the chest (rickety "rosary");
— rickety "bracelets" on wrists;
— stunting or low growth;
— pain in bones and muscles;
— hypotension of muscles when they become weaker;
— fatigue when walking (the child asks to be picked up or to sit);
— dental problems — late eruption, early prolapse, caries, abscesses;
— deformities of the legs — O-shaped (varus) and X-shaped (hallux valgus);
— gait disorder (it looks like a duck's gait);
— craniostenosis is possible, that is, early closure of cranial sutures, which contributes to a limited volume of the skull.
But in adulthood, the disease can also be detected or at least diagnosed. The following will help to suspect him:
— pain in bones, joints and muscles;
— muscle weakness;
— dental problems (frequent abscesses, caries, periodontal disease);
— osteomalacia, that is, softening of bones;
— fractures or incomplete fractures that are accidentally detected by X-ray examination;
— weak extensibility of ligaments and tendons;
— impaired walking (waddling or limping gait);
— impaired joint mobility (enthesopathy, arthrosis);
— hearing loss;
— low height;
— arterial hypertension;
— extraosseous calcification, that is, the deposition of salts in soft tissues.
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