The transition of patients affected by IMDs is a pressing topic, as patients with IMDs currently live longer and have better quality of life. This presents new challenges, as the management of adult patients affected by IMDs and possible complications is not always well defined by specific guidelines or evidence-based medicine but is often based on the experience of centers [20].

The European Reference Network for Hereditary Metabolic Disorders (MetabERN) disseminated a survey on transition programs through 63 centers of MetabERN from 20 countries in Europe [21]. The main challenges identified were the lack of time and the shortage of MD experts in treating adults with IMDs. Conversely, the keys identified for a successful transition program include the presence of a transition coordinator, medical staff entirely dedicated to transition, and targeted training for physicians [21]. An Italian group of clinicians treating PKU published an expert opinion on transition in patients with PKU, in 2022, hightlighting similar critical points [22].

Comparing our findings with those from other countries, the study by Stepien et al. [23] provides valuable insights into the challenges faced in the United States regarding the transition of IMD patients. The main barriers reported in the U.S include the lack of structured transition protocols, insufficient knowledge of IMDs among adult healthcare providers, and disparities in transition readiness due to social and legal differences. These challenges closely mirror those identified in Italy, particularly the limited number of specialized adult metabolic physicians and the absence of standardized transition programs. However, the U.S has seen some progress with the development of transition clinics, multidisciplinary transition teams, and readiness assessment tools such as the Ready Steady Go program. These initiatives aim to ensure a smoother transition process and might serve as a model for improving transition strategies in Italy. Future efforts in Italy should explore the feasibility of implementing similar structured programs to enhance the transition process and ensure better continuity of care.

Although there is a National Coordination Center that has the task of supervision, currently, in Italy, each center is organized individually, without clear guidelines, and without the allocation of specific funds from the government. A total of 16 centers have managed to set up a transition path; 8 have a transition program regulated by an officially approved document in the hospital, which has been ongoing for a range varying between a minimum of 5 and a maximum of 15 years. Among the centers that do not have a transition program, 18 out of 19 expressed interest in establishing one, despite facing individual difficulties and challenges due to the absence of a standardized system. This lack of standardization creates many difficulties, both in creating centers specialized in care for adult patients with IMDs and in creating a structured transition program. Undoubtedly, this can discourage centers treating adult patients from even trying to start a path. A panel of Italian experts produced 8 practical guidelines to obtain an adequate transition program for PKU patients, which could be especially beneficial to centers that are yet to develop one [22].

Even in the centers involved in the management of adult patients with IMDs, there is no homogeneity of care in terms of referred specialized MDs. This aspect underlines the importance of establishing a standardized and shared training path to offer patients the expected standardized quality of care. It is reasonable to assume that transitions may vary depending on the type of disease, given their differing care needs (e.g., risk of decompensation or not). However, addressing each disease group individually would have significantly complicated the study and made the survey more difficult to manage for each specific condition.

One of the major challenges in improving transition programs is the education and training of adult healthcare providers on rare metabolic diseases. Currently, structured educational programs specific to IMDs in adults are limited in Italy, and there is no standardized national curriculum. Training opportunities are often dependent on individual institutions or international collaborations. The development of a dedicated training pathway for adult physicians specializing in IMDs is crucial to ensure continuity of care and proper disease management.

The lack of homogeneity in MDs treating adult patients with IMDs, adversely affects the implementation of effective transition programs. In pediatric centers, this often determines referring patients to various specialists based on their predominant clinical manifestations, rather than to a physician who can serve as a central coordinator, engaging different specialists as needed based on the diverse clinical presentations of IMDs.

Another critical aspect is the funding of transition programs. At present, there are no designated governmental funds allocated specifically for transition services in IMDs in Italy [24]. Funding, when available, often comes from institutional hospital budgets, research grants, or patient advocacy groups [24]. Future efforts should aim to secure stable funding from national healthcare systems, European Union health programs, and philanthropic organizations to establish and sustain structured transition pathways. In Italy, Law 175/2021 assigns responsibility to reference centers for defining a personalized care pathway. This pathway includes the necessary treatments and monitoring for individuals affected by rare diseases, while also ensuring a structured transition from pediatric to adult care. However, practical implementation of this personalized care pathway is lacking.

In 14 out of the 16 centers with a transition program, patients transition at 18, which is the age of consent in Italy. Reviewing the literature, an agreement about the ideal age to start transitioning is yet to be found. Despite the need to agree on age, transition in patients with IMDs should be considered a process rather than a passage, which should occur over an adequate period to give the patient and the family the chance to accommodate the new care setting. To make this process effective, patients (and their respective families) must be informed and made aware early on by the pediatric unit that, as adults, they will be transitioned to a specific center that can better suit the particular needs of their disease as they grow older [25]. The number of joint visits combining both teams should be based on clinical needs and the organization of the centers (1–10).

The extreme variability of the transition paths in Italy is also reflected by the different compositions of the teams caring for adult patients. An MD, even with a different specialty, is always present; dietitians are not always present; dedicated nurses or psychologists are present in only half of the centers; and only 1 center reported having a dedicated biologist to organize and coordinate the transition process.

Considering sociopsychological aspects, only one third of the centers declared routine evaluations of their patients before starting the transition. Unfortunately, the survey did not delve further into the methods used, so we do not know how these centers evaluate these aspects. In 3 centers the degree of patient satisfaction with the transition process is routinely assessed; unfortunately, we do not have data related to the outcome of these evaluations, so at this time, we cannot comment on this matter. All the centers agreed that sharing clinical information for each transitioned patient between pediatric and adult centers efficiently and effectively was feasible, that the skills of the various MDs were recognized in this process, and that adult patients felt better in an environment tailored to their needs. Among the difficulties in maintaining follow-up for both pediatric and adult patients, the main concern that emerged was the lack of a doctor specialized in IMDs to treat adult patients. This again underlines the lack of standardization in the quality of care offered to patients. In addition, there is a lack of psychologists and a lack of space to create specialized clinics.

Among the 19 centers that do not have a transition program, all but one would replicate the pediatric management model, creating an adult center that cares for all IMDs regardless of specific clinical manifestations. These centers identify the desirable age to start the transition at 18, agreeing on what emerged from the centers with a program. Notably, 10 out of 19 centers are already working to start a transition program soon; with these centers, those with a transition program will potentially outnumber those that do not.

The high rate of adults lost to follow-up is another crucial element to be considered, among other reasons, to highlight the necessity of developing a transition program [21]. In fact, out of the 19 centers, only 6 reported losing less than 10% of adult patients. Having a specialized center for adult patients with IMDs, with standardized procedures, personnel, infrastructure, and a program to transition patients from pediatric units to adult units, would promote adequate standardized quality of care, consequently promoting adherence to treatment and medical follow-up of adult patients. In reference to Fig. 3a, it appears that in 6 out of 14 centers with a transition program, the same dietitian who follows pediatric patients with IMDs continues the follow-up for adult patients with IMDs as well. Considering 2 missing data points, 50% of these centers retain the same dietitian for both pediatric and adult patients with IMDs.

On the other hand, Fig. 3b shows that in centers without a transition program the majority of dietitians [7] would assign the nutritional follow-up of adult patients with IMDs to a new dedicated dietitian, whereas only 2 dietitians would maintain nutritional follow-up with the same pediatric dietitian.

As already highlighted, the presence of NBS and the increased life expectancy of patients with IMDs result in a larger number of adult patients in follow-up, leading to an increased workload and the need for specialized skills. This aspect is also relevant among the dietitians and physicians who participated in the survey. In fact, as shown in Tables 2 and 3, the lack of dedicated and trained dietitians for the treatment of adults with IMDs is identified as one of the main issues, both for those with an active transition program and for those without one.

Another relevant aspect is that MDs and dietitians working in centers where there is no transition are concerned with the growing workload and the difficulties in managing typical adult conditions, such as pregnancy. Once again, the lack of standardization in Italy is a critical point in establishing a transition program, as the main difficulties that hinder standartization of adequate structure and personnel trained in IMDs.

The strength of this study is the inclusion of all the main players in treating patients with IMDs, including dietitians and MDs for both pediatric and adult patients; the main aim is to provide, for the first time, an overview of the state of the transition programs in Italy, especially including centers that still do not have a program. Among the limitations of the study, the methodological one. Since this is a survey, the highest level of evidence is the participants' experience. Furthermore, not all doctors who deal with IMDs participated in this study.