Monogenic diseases that can be cured by liver transplantation

Stefano Fagiuoli, Erica Daina, Lorenzo D'Antiga, Michele Colledan, Giuseppe Remuzzi

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

While the prevalence of most diseases caused by single-gene mutations is low and defines them as rare conditions, all together, monogenic diseases account for approximately 10 in every 1000 births according to the World Health Organisation. Orthotopic liver transplantation (LT) could offer a therapeutic option in monogenic diseases in two ways: by substituting for an injured liver or by supplying a tissue that can replace a mutant protein. In this respect, LT may be regarded as the correction of a disease at the level of the dysfunctional protein. Monogenic diseases that involve the liver represent a heterogeneous group of disorders. In conditions associated with predominant liver parenchymal damage (i.e., genetic cholestatic disorders, Wilson's disease, hereditary hemochromatosis, tyrosinemia, α1 antitrypsin deficiency), hepatic complications are the major source of morbidity and LT not only replaces a dysfunctional liver but also corrects the genetic defect and effectively cures the disease. A second group includes liver-based genetic disorders characterised by an architecturally near-normal liver (urea cycle disorders, Crigler-Najjar syndrome, familial amyloid polyneuropathy, primary hyperoxaluria type 1, atypical haemolytic uremic syndrome-1). In these defects, extrahepatic complications are the main source of morbidity and mortality while liver function is relatively preserved. Combined transplantation of other organs may be required, and other surgical techniques, such as domino and auxiliary liver transplantation, have been attempted. In a third group of monogenic diseases, the underlying genetic defect is expressed at a systemic level and liver involvement is just one of the clinical manifestations. In these conditions, LT might only be partially curative since the abnormal phenotype is maintained by extrahepatic synthesis of the toxic metabolites (i.e., methylmalonic acidemia, propionic acidemia). This review focuses on principles of diagnosis, management and LT results in both paediatric and adult populations of selected liver-based monogenic diseases, which represent examples of different transplantation strategies, driven by the understanding of the expression of the underlying genetic defect.

Original languageEnglish
Pages (from-to)595-612
Number of pages18
JournalJournal of Hepatology
Volume59
Issue number3
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Liver Transplantation
Liver
Inborn Genetic Diseases
Crigler-Najjar Syndrome
Inborn Urea Cycle Disorder
Propionic Acidemia
Familial Amyloid Neuropathies
Tyrosinemias
Morbidity
Hepatolenticular Degeneration
Hemochromatosis
Poisons
Organ Transplantation
Mutant Proteins
Liver Diseases
Transplantation
Parturition
Pediatrics
Phenotype
Mutation

Keywords

  • Genetic diseases Inborn
  • Liver transplantation
  • Metabolic diseases
  • Rare diseases
  • Surgical gene therapy

ASJC Scopus subject areas

  • Hepatology

Cite this

Monogenic diseases that can be cured by liver transplantation. / Fagiuoli, Stefano; Daina, Erica; D'Antiga, Lorenzo; Colledan, Michele; Remuzzi, Giuseppe.

In: Journal of Hepatology, Vol. 59, No. 3, 09.2013, p. 595-612.

Research output: Contribution to journalArticle

Fagiuoli, Stefano ; Daina, Erica ; D'Antiga, Lorenzo ; Colledan, Michele ; Remuzzi, Giuseppe. / Monogenic diseases that can be cured by liver transplantation. In: Journal of Hepatology. 2013 ; Vol. 59, No. 3. pp. 595-612.
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