Liver and intrahepatic bile ducts - nontumor
Metabolic diseases
Hereditary tyrosinemia

Topic Completed: 1 May 2012

Revised: 24 February 2020

Copyright: 2002-2020,, Inc.

PubMed Search: Hereditary tyrosinemia[TI] liver

Komal Arora, M.D.
Page views in 2019: 325
Page views in 2020 to date: 48
Cite this page: Arora K. Hereditary tyrosinemia. website. Accessed March 31st, 2020.
Definition / general
  • Type I: autosomal recessive disease caused by deficiency of fumarylacetoacetate hydrolase, the last enzyme in the catabolic pathway of tyrosine; high prevalence (1 per 1,846 births) in eastern (Saguenay-Lac-Saint-Jean) Quebec (GeneReviews: Tyrosinemia Type I [Accessed 27 October 2017])
  • Also called FAH deficiency, hepatorenal tyrosinemia, hereditary tyrosinemia type I, fumarylacetoacetase deficiency, fumarylacetoacetate hydrolase deficiency
  • May be severe, affecting liver, kidneys, nervous system but also clinically heterogeneous, with no correlation between genotype and phenotype
  • Acute form causes hepatic failure in newborns and death by age 1 without treatment (Am J Hum Genet 1990;47:317)
  • Chronic form is milder, with chronic liver disease, renal tubular dysfunction, hypophosphatemia with rickets and increased risk for hepatocellular carcinoma
  • 80% of patients have reversion of mutant alleles in hepatocytes, associated with better prognosis; i.e. no dysplasia, no carcinoma (Hum Pathol 2003;34:1313)
Diagrams / tables

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Tyrosine metabolic pathway

  • 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) reduces accumulation of toxic metabolites
  • Possibly liver transplantation (Pediatr Transplant 2011;15:400)
Microscopic (histologic) description
  • Hepatocellular degeneration with focal fatty change, particularly in regenerative nodules
  • Pseudorosettes, cholestasis, fibrosis, cirrhosis
Microscopic (histologic) images

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Mosaic FAH expression in livers from patients with acute, subacute and chronic disease:
(A) Acute patient: liver explant from 6 month old patient reveals micronodular cirrhosis with an occasional small focus of reversion when immunostained with anti-FAH antibody
(B) Subacute patient: liver explant from 27 month old patient reveals mixed macronodular micronodular cirrhosis; reversion occurs primarily in macronodules
(C) Chronic patient: mixed macronodular and micronodular cirrhosis with single well delimited carcinomatous nodule in explanted liver
(D) Same patient as (C): immunostaining of adjacent section with anti-FAH reveals extensively reverted nodules; note that carcinomatous nodule remains unstained
(E) Chronic patient: liver explant from patient at 10 years, 9 months reveals relatively well preserved architecture with little fibrosis
(F) Same patient as (E): immunostaining of adjacent section reveals extensive reversion

Electron microscopy description
  • Cholestasis, lipid droplets, increased endoplasmic reticulum, abnormal mitochondria
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