World Day

Rare diseases: the odyssey of 100,000 with an undiagnosed condition

It is not a status that results from an absence, but a real condition, which impacts on access to treatment and the difficulty of taking charge

by Annalisa Scopinaro*

29 April 2026

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4' min read

Translated by AI

Versione italiana

4' min read

Translated by AI

Versione italiana

29 April is World Rare Disease Day, established to raise awareness among citizens and institutions about a clinical condition that - according to estimates by the National Institutes of Health (NIH) - now affects 6% of people with a rare disease. In Italia, there are about 2 million rare diseases and, consequently, among them there are at least 100,000 people living with an undiagnosed condition. This is not simply a status resulting from an absence, but a real condition, which has an impact on access to therapies and the difficulty of taking care of them. The main consequence, combined with a lack of codification in healthcare systems, concerns a high risk of inappropriate care, with individuals and families experiencing an endless and tortuous pathway towards a diagnosis that does not arrive, between consultations with different specialists, continuous visits, ineffective therapies and, in most cases, a non-negligible impact on mental health.

People living with an undiagnosed disease are currently divided into two categories. 'Undiagnosed' refers to a patient for whom a diagnostic test is not yet available because the disease has not yet been characterised and the cause has not yet been identified . "Pending diagnosis" refers to a patient living with an undiagnosed condition that should be identified, but has not been identified because the patient has not been referred to the appropriate specialist, due to common but misleading symptoms or an unusual clinical presentation of an already known rare condition .

In this regard, it is worth remembering that the diagnostic odyssey is still unfortunately very common among people who have a rare disease. In addition to being rarely found, in fact, rare diseases have symptoms and manifestations that also vary from person to person, thus making them even more difficult to diagnose. The average time for a diagnosis is more than 4 years, but can be up to 7 and in some cases much longer. The longer this odyssey takes, the more damaging the consequences are for the individuals and families who experience it, but also for the health systems, which pay the price for inappropriate care that results in unnecessary visits and examinations, longer waiting lists, staff costs, interregional mobility, and so on.

This is why, in order to speed up the time it takes to diagnose rare diseases, it is essential to act at system level through a strategy that includes investment in the training of general practitioners and paediatricians of free choice, who must be ready to recognise the so-called 'red flags', i.e. those symptoms that trigger the suspicion of a rare disease; integration in clinical practice, also in public health, of innovative diagnostic technologies, which are increasingly precise and sophisticated also thanks to the use of genomics; uniformity of all regions in the implementation of neonatal screening; sharing and interoperability of data between different institutions and scientific collaboration at international level.

In this sense, in 2016 the National Center for Rare Diseases of the Istituto Superiore di Sanità, together with the US National Institute of Health (NIH), launched a national programme on undiagnosed rare diseases, called 'Undiagnosed Rare Diseases: a joint Italy-US project'.

The national programme is part of the Undiagnosed Diseases Network InternationaI-UDNI, an international network of clinicians, researchers and patients founded in 2014, in which Uniamo, the Italian Federation of Rare Diseases, also participates as a partner.

The diagnostic pathway is one of the focuses of Uniamo's strategy and activities, whose commitment on this issue is exercised through two channels. On the one hand, the Federation, through its free SAIO service (Servizio di Ascolto, Informazione e Orientamento - Listening, Information and Orientation Service) provides specialised psychological support and helps people to find their way among the SSN structures in order to identify the correct reference centre in the event of an absence of diagnosis or a still uncertain diagnosis. On the other hand, Uniamo works on the institutional level through participation in specific tables (such as the Ministry of Health's SNE table), political solicitation in order to identify appropriate and uniform diagnosis paths throughout the territory, and collaboration with scientific societies in order to exploit and systemise the most recent technological innovations in the diagnostic field. Also important in this regard is the dissemination of knowledge among patient associations of the ERNs (European Reference Networks), the networks that link specialised health centres throughout Europe to improve the diagnosis and treatment of rare or complex diseases.

On the diagnostic pathway, several steps forward have been taken at the regulatory level in recent years, just think of Law 167/2016, which made extended neonatal screening mandatory throughout the country. Also from the point of view of awareness and training of doctors and specialists, CME courses on rare diseases have increased and projects aimed at speeding up diagnosis are increasingly numerous. All this is still not enough, however, and there are still many goals to be achieved in this field: World Rare Disease Day reminds us of this every year.

*President Uniamo Italian Federation of Rare Diseases