The frequency of rare and monogenic diseases in pediatric organ transplant recipients in Italy

Abstract

Background Rare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000. For most of them, clinical symptoms and signs can be observed at birth or childhood. Approximately 80% of all rare diseases have a genetic background and most of them are monogenic conditions. In addition, while the majority of these diseases is still incurable, early diagnosis and specific treatment can improve patients’ quality of life. Transplantation is among the therapeutic options and represents the definitive treatment for end-stage organ failure, both in children and adults. The aim of this paper was to analyze, in a large cohort of Italian patients, the main rare genetic diseases that led to organ transplantation, specifically pointing the attention on the pediatric cohort. Results To the purpose of our analysis, we considered heart, lung, liver and kidney transplants included in the Transplant Registry (TR) of the Italian National Transplantation Center in the 2002–2019 timeframe. Overall, 49,404 recipients were enrolled in the cohort, 5.1% of whom in the pediatric age. For 40,909 (82.8%) transplant recipients, a disease diagnosis was available, of which 38,615 in the adult cohort, while 8,495 patients (17.2%) were undiagnosed. There were 128 disease categories, and of these, 117 were listed in the main rare disease databases. In the pediatric cohort, 2,294 (5.6%) patients had a disease diagnosis: of the 2,126 (92.7%) patients affected by a rare disease, 1,402 (61.1%) presented with a monogenic condition. As expected, the frequencies of pathologies leading to organ failure were different between the pediatric and the adult cohort. Moreover, the pediatric group was characterized, compared to the adult one, by an overall better survival of the graft at ten years after transplant, with the only exception of lung transplants. When comparing survival considering rare vs non-rare diseases or rare and monogenic vs rare non-monogenic conditions, no differences were highlighted for kidney and lung transplants, while rare diseases had a better survival in liver as opposed to heart transplants. Conclusions This work represents the first national survey analyzing the main genetic causes and frequencies of rare and/or monogenic diseases leading to organ failure and requiring transplantation both in adults and children.

The role of genetic testing in the diagnostic workflow of pediatric patients with kidney diseases: the experience of a single institution

“…The most recent analyses on adult and pediatric patients, who have received a kidney transplant or are included in the transplant waiting list or are present in the registries of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) indicate that up to 27% of them are undiagnosed at the time of transplantation [ 7 ]. In line with these data, by analyzing the Transplant Registry of the Italian National Transplant Center, we recently reported that approximately 17.2% of the pediatric cohort was without a clear clinical diagnosis [ 6 ]. In addition, when considering the different disease categories, the great majority was affected by rare conditions and up to 50% by a monogenic disease [ 6 ].…”

“…In line with these data, by analyzing the Transplant Registry of the Italian National Transplant Center, we recently reported that approximately 17.2% of the pediatric cohort was without a clear clinical diagnosis [ 6 ]. In addition, when considering the different disease categories, the great majority was affected by rare conditions and up to 50% by a monogenic disease [ 6 ]. These results suggest that genetic screening may be a valuable addition for increasing the diagnostic rate.…”

“…Approximately 30% of children with chronic kidney disease (CKD) suffer from a monogenic condition, a percentage increasing when considering children with end-stage renal disease (ESRD) [ 5 , 6 ]. Many of these children remain undiagnosed at the time of transplantation [ 4 , 6 , 7 ]. Reaching a diagnosis for these patients not only implies the end of a diagnostic odyssey, but presents several advantages for prognosis, management, and treatment.…”

Rare and unknown diseases are a modern trend in medicine

“…), распространенность 1 пациент на 10 000 человек населения является достаточным показателем для РЗ [21]. Кроме того, некоторым РЗ присуща определенная эндемичность и специфич ность для конкретной популяции, несмотря на их редкую встречаемость [4].…”

“…Довольно часто эти заболевания носят семейный характер. Безусловно, медико-генетические и ла бораторно-генетические методы исследования и, в частности, новые технологии секвенирования ДНК и РНК расширили границы понимания мно гих редких и малоизученных заболеваний, а также помогли в установлении ранее не известных и не описанных нозологических форм [4]. Нередко они ассоциированы с тяжелой клинической картиной.…”