On the occasion of the International Day of Rare Diseases on February 28, Why Doctor met Dr. Nadia Belmatoug, specialist in Gaucher disease which affects 500 people in France. It provides an update on this disease and more generally on the difficulties encountered in the diagnosis and management of these rare diseases.
– Why Doctor: You are a specialist in a rare disease, Gaucher’s disease, which affects around 500 people in France. Can you explain to us what this disease is?
Dr Nadia Belmatoug : It is a disease which affects the lysosomes, small bags which are in the cytoplasm of the cells and which contain enzymes which will be used to cut out the substances at the end of their life which must be degraded in order to be eliminated. In this genetic disease, these enzymes are deficient and the substances will accumulate in the lysosomes and clog them, which disrupts the cellular machinery by causing inflammation, fibrosis and other irreversible damage. Lysosomal storage diseases are chronic, degenerative and disabling
– How does Gaucher’s disease affect the state of health of patients?
The infiltrated organs – this may concern the spleen, the central nervous system, the bones, the liver – will grow, increase in volume. It is a disease that can begin in childhood, even in utero, and which worsens over time. This chronic evolution is accompanied by accidents which mark a worsening of the patient’s condition. It is during these clinical events that the diagnosis will be made.
These are very heterogeneous diseases that can be serious in some patients, less so in others. Those that affect the central nervous system are the most serious because they result in damage to cognitive functions or the occurrence of disabilities. In Gaucher’s disease, it is the degradation of blood cells which is concerned and the substrates accumulate in the spleen, the liver or the bones, more rarely in the central nervous system.
– How can such a heterogeneous disease be diagnosed?
The diagnosis is most often made from the observation of a large spleen or a large liver which leads to a drop in red blood cells and platelets. We therefore have bleeding, hematomas, a risk of hemorrhage, anemia or bone pain. But the spleen is a deep organ that is difficult to palpate, and liver lumps can have multiple origins. We therefore first think of common diseases before thinking of a rare disease. This is why there is a significant risk of diagnostic error.
– This difficulty in making a diagnosis, what are its consequences?
The main consequence is that the diagnosis is often made 5 or even 10 years after the appearance of the first symptoms. Patients who consult but do not see their condition improve do not understand their doctor telling them “I don’t know” and feel abandoned. It is for this reason that the task of general practitioners is complicated in these diseases. When they cannot find the cause of the symptoms, they must have a culture of doubt which pushes them to refer the patient to reference centers which exist for these diseases, there are more than a hundred centers in France.
– What are the treatments for this Gaucher disease?
At the beginning, around 1990, there was a treatment derived from the human placenta but it was only given for serious cases because of the doubts born of the business of growth hormones. Then, around 1996, there were enzyme replacement treatments: the missing enzyme is given through intravenous injections, every 15 days, for life and in a hospital setting or hospitalization at home. Fortunately, research has just enabled the development of a new treatment based on a substrate inhibitor: we no longer give the missing enzyme, we treat the non-degraded substances directly. The advantage is that this treatment can be administered orally, but in some cases there may be contraindications. Patients are 100% covered and despite the high cost of these treatments, there have fortunately never been any limits imposed on its prescription by the health authorities.
– But are all patients with this disease diagnosed and treated today?
As we now have these safe and effective treatments, it is even more unfortunate to miss a diagnosis, which still often happens. The difficulty in rare diseases is that there are only a few experts. As a rheumatologist myself, I came to be interested in Gaucher’s disease from the case of a patient who had symptoms and a large spleen and who I learned had other cases in her family including a sister who had been diagnosed in hospital with the disease. I became interested in this case and from the information I had gathered, I was able to make the diagnosis and then I developed a database, worked with patient associations and participated in work on treatments.
– Has the 2018-2022 rare disease plan led to new progress?
Yes, and they are much larger than in previous plans. The first enabled the setting up of reference centres, the second that of “rare diseases” health networks which bring together the reference centres. This third plan has made it possible to make progress on the creation and use of databases to better understand these diseases and on the establishment of a national treatment protocol. Because the best way to avoid diagnostic error is to improve the course of care and allow better access for health professionals to the information we have today on these diseases.
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