- 作者：Jean Larochelle ; Fern ; o Alvarez ; Jean-Fran?ois Bussi¨¨res ; Isabelle Chevalier ; Louis Dallaire ; Jos¨¦e Dubois ; Fr¨¦d¨¦ric Faucher ; Daphna Fenyves ; Paul Goodyer ; Andr¨¦ Grenier ; Elisabeth Holme ; Rachel Laframboise ; Marie Lambert ; Sven Lindstedt ; Bruno Mar ; a ; Serge Melan?on ; Aicha Merouani ; John Mitchell ; Guy Parizeault ; Luc Pelletier ; et al.
- 关键词：AFP ; alpha-foetoprotein ; ALA ; delta-aminolevulinic acid ; ALT ; alanine aminotransferase ; FAH ; fumarylacetoacetate hydrolase ; HT1 ; hereditary tyrosinemia ; type 1 ; 4HPL ; 4-hydroxyphenyllactate ; 4HPP ; 4-hydroxyphenylpyruvate ; PBG ; porphobilinogen ; SA ; succiny
- 刊名：Molecular Genetics and Metabolism
- 出版年：2012
- 出版时间：September-October, 2012
- 年：2012
- 卷：107
- 期：1-2
- 页码：49-54
- 全文大小：538 K
Background
Hepatorenal tyrosinemia (HT1, fumarylacetoacetate hydrolase deficiency, MIM ) can cause severe hepatic, renal and peripheral nerve damage. In Qu¨¦bec, 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 Qu¨¦bec since 1994.Methods
We recorded the clinical course of 78 Qu¨¦bec 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.
Findings
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.
Interpretation
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.