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

Tiziana Vaisitti ,Silvia Catalano ,Elisa Benetti ,Daniele De Angelis ,Eliana Gotti ,Serena Abbate ,Massimo Torre ,Massimo Boffini ,Marco Schiavon ,I Fontana ,Licia Peruzzi ,D Peritore ,Sara Testa ,D Pinelli ,Marisa Varrenti ,Antonio Amodeo ,A Ricci ,Letizia Lombardini ,Marco Sciveres ,Amedeo Terzi ,Marco Spada ,Luca Ragni ,Enrico Gringeri ,Paola Mapelli ,Angelo Di Giorgio ,Alessandro Bertani ,Giorgia Comai ,Adele Mitrotti ,Gino Gerosa ,Carlo Pace Napoleone ,Massimo Cardillo ,Camilla Poggi ,Silvia Deaglio ,Giuseppe Limongelli ,Luca Dello Strologo ,Antonio Amoroso

doi:10.1186/s13023-021-02013-x

Abstract

BackgroundRare 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.ResultsTo 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.ConclusionsThis 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.

Highlights

Rare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000
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
N. of transplants Without diagnosis of the original disease With diagnosis Adults Pediatrics N. of pediatric disease categories N. of pediatric diseases included in the rare disease catalogs N. of pediatric patients diagnosed with a rare disease N. of pediatric patients diagnosed with a monogenic disease

Summary

Introduction

Rare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000. 80% of all rare diseases have a genetic background and most of them are monogenic conditions. Rare diseases are chronic and debilitating disorders affecting a small number of people compared to the general population, with small differences in definition. There are geographical issues, as diseases that are generally rare can be frequent in a specific population. 80% of all rare diseases are genetic in origin and most of them display a family distribution compatible with a monogenic origin [4, 5], even though in a proportion of disorders the causative gene remains elusive [5, 6]. The recent evolution and broader application of sequencing technologies have revealed the genetic causes of novel rare disease and led to the identification of new variants responsible for previously defined disorders [7]

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