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Congenital diarrhoeal disorders: advances in this evolving web of inherited enteropathies

Key Points

  • Congenital diarrhoeal disorders (CDDs) are a group of rare inherited enteropathies with a typical onset early in the life

  • These disorders are challenging clinical conditions because of the severity of the clinical picture and the broad range of diseases in differential diagnosis

  • To simplify the approach to these conditions, a classification in four groups according to the main pathogenetic mechanism has been proposed

  • The number of conditions included within the CDDs group has gradually increased, and many new genes have been identified, opening new diagnostic and therapeutic perspectives

  • Clinically actionable molecular methods to diagnosis CDDs, and other monogenic disorders, have markedly improved in recent years

  • Continued research is focused on identifying novel CDDs, and to define in detail the pathogenesis of established disorders that might provide novel therapeutic options to ameliorate morbidity and mortality

Abstract

Congenital diarrhoeal disorders (CDDs) represent an evolving web of rare chronic enteropathies, with a typical onset early in life. In many of these conditions, severe chronic diarrhoea represents the primary clinical manifestation, whereas in others diarrhoea is only a component of a more complex multi-organ or systemic disorder. Typically, within the first days of life, diarrhoea leads to a life-threatening condition highlighted by severe dehydration and serum electrolyte abnormalities. Thus, in the vast majority of cases appropriate therapy must be started immediately to prevent dehydration and long-term, sometimes severe, complications. The number of well-characterized disorders attributed to CDDs has gradually increased over the past several years, and many new genes have been identified and functionally related to CDDs, opening new diagnostic and therapeutic perspectives. Molecular analysis has changed the diagnostic scenario in CDDs, and led to a reduction in invasive and expensive procedures. Major advances have been made in terms of pathogenesis, enabling a better understanding not only of these rare conditions but also of more common diseases mechanisms.

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Acknowledgements

Grants from Regione Campania, DGRC 1901/09 and Agenzia Italiana del Farmaco (AIFA) MRAR08W002 (to R.B.C.), and from NIDDK (#DK083762), and CIRM (RT2-01985) (to M.G.M.) and Italian Telethon Foundation (TGT11A4) (to R.B.) are gratefully acknowledged. The authors thank V. Pezzella for help on text editing.

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Correspondence to Roberto Berni Canani.

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Canani, R., Castaldo, G., Bacchetta, R. et al. Congenital diarrhoeal disorders: advances in this evolving web of inherited enteropathies. Nat Rev Gastroenterol Hepatol 12, 293–302 (2015). https://doi.org/10.1038/nrgastro.2015.44

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