Tyrosinemia: A Review |
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Authors: | Pierre A Russo Grant A Mitchell Robert M Tanguay |
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Institution: | Department of Pathology, The Children's Hospital of Philadelphia, 324 S. 34th Street, Philadelphia, PA 19104, USA, US Department of Pediatrics, Service de Génétique Médicale, H?pital Ste-Justine, 3175 C?te Ste-Catherine, Montréal, Quebec, Canada H3T 1C5, CA Laboratory of Cell and Developmental Genetics, Department of Medicine, Universite Laval and Centre de Recherche de l'Universite Laval, Ste Foy, Quebec, Canada G1K 7P4, CA
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Abstract: | Hypertyrosinemia encompasses several entities, of which tyrosinemia type I (or hepatorenal tyrosinemia, HT1) results in the
most extensive clinical and pathological manifestations involving mainly the liver, kidney, and peripheral nerves. The clinical
findings range from a severe hepatopathy of early infancy to chronic liver disease and rickets in the older child; gradual
refinements in the diagnosis and medical management of this disorder have greatly altered its natural course, mirroring recent
advances in the field of metabolic diseases in the past quarter century. Hepatorenal tyrosinemia is the inborn error with
the highest incidence of progression to hepatocellular carcinoma, likely due to profound mutagenic effects and influences
on the cell cycle by accumulated metabolites. The appropriate follow-up of patients with cirrhosis, the proper timing of liver
transplantation in the prevention of carcinoma, and the long-term evolution of chronic renal disease remain important unresolved
issues. The introduction of a new pharmacologic agent, NTBC, holds the hope of significantly alleviating some of the burdens
of this disease. Mouse models of this disease have permitted the exploration of newer treatment modalities, such as gene therapy
by viral vectors, including ex vivo and in utero methods. Finally, recent observations on spontaneous genetic reversion of
the mutation in HT1 livers challenge conventional concepts in human genetics.
Received November 15, 2000; accepted December 7, 2000. |
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Keywords: | : tyrosinemia type I cirrhosis fumarylacetoacetate hydroxylase deficiency |
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