Rare diseases and genetic tests: tests necessary for diagnosis will be paid for (delaying it)

Silvia, 11 years old, was a mysterious illness until four years ago, when it was discovered that it has the CTNNB1 Syndrome (name of the mutated gene), a very rare and insidious pathology from which one suffers twenty children in Italy and around 300 in the world. Her mother Mirella says: «My daughter was ill, but she couldn’t understand what was wrong despite the many tests carried out in hospitals throughout Italy.

The diagnostic odyssey is over after eight years thanks to a genetic testL’exome analysis: knowing the name of the disease, even if there is no cure to date, has allowed us to take action with other families to stimulate researchin the hope that they are at least found of treatments to improve the quality of life of children.”

Sick people looking for a diagnosis (and a cure)

Like Silvia, there are others sick people looking for a diagnosis (and a cure). Today, thanks also to the technological revolution that has affected genetic analysis in recent years and genomics significantly reducing costs is possible in several cases identify genetic mechanisms more quickly underlying many diseases. And the first step towards taking charge of the patient and to understand if there is a cure or the possibility of developing new therapies.
But the sequencing of the exome and other genetic tests fundamental for the diagnosis of rare and very rare diseases are not included among the specialist outpatient services that are available to patients paid by the National Health Service, as they are currently do not fall within the essential levels of assistance (Leah).
What if up to now it has however been possible to prescribe these genetic tests exemptlythanks to the use of a generic code, soon they could pay Not having been inserted in new nomenclature of outpatient specialistswhich will come into force in January 2025 after yet another postponement.

Revolution in genetics, updating the essential levels of care

Yet more than a year ago the Italian Society of Human Genetics (Sigu) had raised the alarm. «As a scientific society we have pointed out that there are some prescriptive inconsistencies – explains Daniela Zuccarello, medical geneticist at the Clinical Genetics Operational Unit of the University Hospital of Padua -. For example, trio exome sequencingexam that today allows you to investigate thousands of genes to locate potential genetic anomalies, was not included in the previous Lea as it was not available at the beginning of the 2000s; subsequently, “exome analysis” was never introduced as a specific code, even though we geneticists, to prescribe the test paid for by the Health Service, used a generic “DNA sequencing” codewhich however it was eliminated in the new version of the Lea nomenclator of 2017, but whose setting dates back to 2014″.
«In its place, they were introduced codes that allow small groups of genes to be analyzed; but in 10 years, thanks to new molecular technologies, there has been a revolution in genetics: today it no longer makes sense to analyze one or a few genes at a time, both from an economic and time saving point of view. Because of this, the new Lea benefits, although they have not yet come into force, are already inadequate And they need to be updated with the inclusion of investigations that we now use daily, such as exome analysis, the analysis of DNA circulating fetus, preimplantation genetic diagnosis”.

10 thousand known rare diseases (but free investigations for only a thousand)

When the new tariff nomenclature comes into force, another problem may explode. «In case of suspicion of a rare diseaseto prescribe the genetic tests useful for identifying it in exemption, the pathology must be present in a specific list (Prime Ministerial Decree Lea 2017, Annex 4 – Medical genetics, ed) That contains approximately one thousand genetic diseases compared to over ten thousand pathologies known so far, and the specific exemption code must be used. Practically, if the pathology is not on the list, it will not be possible to prescribe in exemption on the NHS recipe certain necessary, very expensive analyses. But it is impossible to create a code for every genetic disease – underlines Dr. Zuccarello –. It would be appropriate, however, to group rare diseases by organ or type, for example, diseases of the eye, liver, bones, so that the geneticist, within those groups, can prescribe the appropriate tests.”

Update the list based on the rating Orpha code

Yet the law no. 175/2021 (Consolidated Law on rare diseases, art. 4, paragraph 4) provides that, to protect the health of rare disease patients, pending the completion of the Lea update procedurea Decree of the Minister of Health (in agreement with the Minister of Economy) updates the list of pathologiesidentified by the National Center for Rare Diseases of the Higher Institute of Health, based on the classification Orpha code, present on the Orphanet portal. To date it has not been issued.

Discrimination between patients based on residence

The Regions with accounts in order they can employ own resources to ensure residents performance – including genetic tests – in extra Lea mode, i.e. not included in the essential levels of assistance. The Regions in the recovery plan (almost all southern regions) cannot do it. It’s not just this discrimination between patients, but yesI also run another risk, to be avoided. Dr. Zuccarello reports this: «In recent months the Regions have been developing their own Regional catalog of specialist services: it would be important for all of them to license the same scheme of services linked to the branch of genetics, in order to avoid unequal treatment in providing exams to patients resident in other Regions. In fact, if a Region remunerates some genetics services more expensively, there is a real risk that non-residents will have to pay the economic difference in the cost – the geneticist points out -. This is how they are created further inequalities between rare disease patients from different regions».

Fetal DNA and preimplantation diagnosis

«They stay outside the essential levels of assistance prenatal genetics performance at this point in use for years in our country, but which are the almost exclusive prerogative of private healthcare – reports Dr. Zuccarello –. Despite Sigu’s repeated requests to the Lea updating Commission, fundamental genetic investigations such asanalysis of circulating fetal DNA (highly sensitive non-invasive screening which is performed in the first months of pregnancy and which avoids the use of invasive procedures) and preimplantation genetic diagnosis useful
to diagnose genetic anomalies of the embryo before transfer to the uterus (in the Pma, ed) avoiding the use of therapeutic termination of pregnancy in the second trimester – underlines the geneticist -. This creates disparity between couples of future parents who can or cannot afford to pay for the service privately.”