Rare diseases affect more than 3 million French people, but they are so numerous and different that their diagnosis often takes too many years.
It’s a strange paradox: rare diseases are very common. A disease is described as “rare” when it affects less than one person in 2,000, or just under 34,000 people across France. While everyone knows about Duchenne muscular dystrophy or cystic fibrosis, many other rare pathologies have no media visibility or even remain unknown to a large number of healthcare professionals. Nothing is surprising when we see how numerous these diseases are. Orphanet, an information platform on rare diseases, coordinated by Inserm, lists more than 6,000 diseases that affect about 3 million people and are in fact one of the leading causes of pathology in France.
Years without potentially damaging knowledge
Although they differ in many aspects – origin, frequency, manifestations, etc. –, they often share common points: they are chronic, disabling and, in 95% of cases, do not benefit from any curative treatment. “Another similarity is that they are often accompanied by a long delay in diagnosis, which exceeds four years for one in four people.”notes Cécile Foujols-Gaussot, Vice President Alliance for Rare Diseases. For Alice Salomone, who suffers from a MYT1L gene anomaly that leads to overall developmental delay, language disorders and other behavioral, coordination, etc. disorders, she had to wait until the age of 7.5 to finally be diagnosed. “The first symptoms appeared around two years ago, he remembers Valérie Salomone, his mother, but the pediatrician who followed her dissuaded us. When she started school, her limitations became more apparent. However, there is still no advanced medical cause. A psychologist consulted at the center for early medical-social action (CAMSP) even mentioned the lack of parental supervision! » Finally, through the Autism Resource Center (ARC), the situation was resolved and for the first time the interest in conducting genetic testing was discussed. Five years after the first suspicions, the diagnosis was finally made.
For Pauline, the wait lasted seven years. The girl suffered from lameness from the age of eight – first due to a cold in her hip – and then her general condition worsened and she was struck by unbearable pain. “We exchanged consultations with doctors, in the hospital, in the emergency room, reports Amélie, her mother, without any cause. » A young girl, misunderstood, isolates herself, eventually dropping out of school during her fifth yeare then voluntarily poisoned himself with drugs in July 2020. “Cry for help”, deciphers his mother. Far from accelerating the investigation into the origins of his pain, this episode instead tends to psychiatrise his treatment. “I fought against medical teams who wanted to place him in psychiatry, and I asked to stay in internal medicine. I was even considered a dysfunctional mother and faced threats to report child welfare. I finally had the intuition of a rare disease. » Doing her best, Amélie manages to convince the doctors at the referral center at the Necker Hospital in Paris to visit Pauline. There, experts immediately notice an abnormal heart rhythm. Pauline underwent emergency surgery in the Paris region for a double bypass and implantation of an aortic and carotid prosthesis. Finally, after seven years of wandering, the diagnosis is made: Pauline suffers from Takayasu’s disease, a pathology that affects one in 1 to 2 million people and is characterized by inflammation of the arteries. “If she had been taken care of earlier, she would be physically and mentally different today”the mother laments.
Democratize procedures
Why do we have to wait so long to get a diagnosis? “Firstly because 80% of rare diseases are of genetic origin and only 60,000 sequencings are carried out every year, including the families of affected people, explains Professor Guillaume Canaud, a nephrologist at the Necker Hospital and responsible, together with Professor Agnès Linglart, for coordinating the 4.e the national plan for rare diseases (PNMR), launched this year. Difficulties concern both access to tests and geneticists, as well as the delivery time of results. » Faced with a problem of unknown origin suspected to have a genetic cause, the first step consists of referring the patient to a genetic center, taking samples and sending them to one of the only two national platforms that can analyze them. “One of the goals of 4e the national plan is to democratize molecular tests by opening up opportunities for other players to conduct them. These can be, for example, oncology centers or private players in biological analysis,” continues Professor Canaud. The second step: Doctors either run tests on targeted genes – a technique called a panel – or complete DNA analysis, via exome and genome sequencing techniques. “Then we find ourselves with astronomical data to analyzedeveloped by Professor Canaud. For this, experts, or bioinformaticians, are needed, of which there are not enough. » Here too, PNMR intends to push the boundaries by upgrading this profession to make it more attractive. Then all detected anomalies must be interpreted by hospital geneticists: “If other health professionals, not just geneticists, could validate the tests, the cycle of screening would be accelerated”. This would undoubtedly prevent many patients from ever receiving the results of their molecular analyses. Of the 10 to 12 patients I see every day, the vast majority have never heard of the results, Guillaume Canaud testifies.
Develop a culture of doubt
Another important issue in improving the time of diagnosis is the possibility of carrying out treatment as early as possible. “This is, for example, the case of phenylketonuria, which, if not treated very early, leads to mental retardation and neuropsychiatric disordersunderscores Cécile Foujols-Gaussot. Thanks to a systematic examination since 1972, it is possible to implement a specific diet that prevents the development of the disease. » In 2023, the health authorities increased from 6 to 13 the number of examinations carried out at birth with the so-called “Guthrie” test. The problem is that there are pathologies for which there is treatment, but which are not yet part of neonatal screening. This is the case with spinal muscular atrophy (SMA), for which three treatments are available. “Tests are not performed before symptoms appear, laments Professor Canaud. However, it is a disease that progresses rapidly once symptoms appear. » PNMR proposes to significantly increase the number of pathologies detected at birth in order to limit this type of situation. By comparison, Italy scores more than 40.
Finally, on the physician side, people with rare diseases and their loved ones want to see a culture of doubt strengthened to reduce diagnostic drift. “When they cannot find the origin of the disease or unusual symptoms, they should always ask themselves if it could be a rare disease”hopes Cécile Foujols-Gaussot. Healthcare workers can especially rely on the RDK (Rare Disease Knowledge) application, jointly developed by Inserm, which, based on symptoms, age and gender, suggests a list of pathologies with a percentage of probability and points to expert centers capable of making a diagnosis. » As for the general public, anyone with a diagnosis and questions can contact the Rare Disease Information Line on 0 800 40 40 43 for information and guidance.