title: Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec.
abstract: BACKGROUND
  Hepatorenal tyrosinemia (HT1, fumarylacetoacetate hydrolase deficiency, MIM 276700) can cause severe hepatic, renal and peripheral nerve damage. In Québec, HT1 is frequent and neonatal HT1 screening is practiced. Nitisinone (NTBC, Orfadin ®) inhibits tyrosine degradation prior to the formation of toxic metabolites like succinylacetone and has been offered to HT1 patients in Québec since 1994.
  
  
  METHODS
  We recorded the clinical course of 78 Québec HT1 patients born between 1984 and 2004. There were three groups: those who never received nitisinone (28 patients), those who were first treated after 1 month of age (26 patients) and those treated before 1 month (24 patients). Retrospective chart review was performed for events before 1994, when nitisinone treatment began, and prospective data collection thereafter.
  
  
  RESULTS
  No hospitalizations for acute complications of HT1 occurred during 5731 months of nitisinone treatment, versus 184 during 1312 months without treatment (p<0.001). Liver transplantation was performed in 20 non-nitisinone-treated patients (71%) at a median age of 26 months, versus 7 late-treated patients (26%, p<0.001), and no early-treated patient (p<0.001). No early-treated patient has developed detectable liver disease after more than 5 years. Ten deaths occurred in non-nitisinone treated patients versus two in treated patients (p<0.01). Both of the latter deaths were from complications of transplantation unrelated to HT1. One probable nitisinone-related event occurred, transient corneal crystals with photophobia.
  
  
  CONCLUSIONS
  Nitisinone treatment abolishes the acute complications of HT1. Some patients with established liver disease before nitisinone treatment eventually require hepatic transplantation. Patients who receive nitisinone treatment before 1 month had no detectable liver disease after more than 5 years.
authors.affiliation: Centre de santé et de services sociaux de Chicoutimi, 305, rue Saint-Vallier, CP 5006, Chicoutimi, Québec, Canada G7H 5H6.
authors.forename: Jean
authors.initials: J
authors.lastname: Larochelle
authors.forename: Fernando
authors.initials: F
authors.lastname: Alvarez
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bussières
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chevalier
authors.forename: Louis
authors.initials: L
authors.lastname: Dallaire
authors.forename: Josée
authors.initials: J
authors.lastname: Dubois
authors.forename: Frédéric
authors.initials: F
authors.lastname: Faucher
authors.forename: Daphna
authors.initials: D
authors.lastname: Fenyves
authors.forename: Paul
authors.initials: P
authors.lastname: Goodyer
authors.forename: André
authors.initials: A
authors.lastname: Grenier
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Holme
authors.forename: Rachel
authors.initials: R
authors.lastname: Laframboise
authors.forename: Marie
authors.initials: M
authors.lastname: Lambert
authors.forename: Sven
authors.initials: S
authors.lastname: Lindstedt
authors.forename: Bruno
authors.initials: B
authors.lastname: Maranda
authors.forename: Serge
authors.initials: S
authors.lastname: Melançon
authors.forename: Aicha
authors.initials: A
authors.lastname: Merouani
authors.forename: John
authors.initials: J
authors.lastname: Mitchell
authors.forename: Guy
authors.initials: G
authors.lastname: Parizeault
authors.forename: Luc
authors.initials: L
authors.lastname: Pelletier
authors.forename: Véronique
authors.initials: V
authors.lastname: Phan
authors.forename: Piero
authors.initials: P
authors.lastname: Rinaldo
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Scott
authors.forename: Charles
authors.initials: C
authors.lastname: Scriver
authors.forename: Grant A
authors.initials: GA
authors.lastname: Mitchell
mesh_terms: D002648:Child; D002675:Child, Preschool; D003512:Cyclohexanones / Q000009:adverse effects / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation; D015997:Neonatal Screening; D009579:Nitrobenzoates / Q000009:adverse effects / Q000627:therapeutic use*; D011792:Quebec; D016896:Treatment Outcome; D020176:Tyrosinemias / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy
chemical_list: D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D009579:Nitrobenzoates; C077073:nitisinone