title: Hereditary tyrosinemia type 1 in Turkey: twenty year single-center experience.
abstract: BACKGROUND
  Hereditary tyrosinemia type 1(HT1) is a chronic disorder leading to severe hepatic, renal and peripheral nerve damage if left untreated. Despite nitisinone treatment HT1 still carries the risks of hepatocellular carcinoma (HCC) and neuropsychological outcome.
  
  
  METHODS
  A retrospective single center study was carried out based on the phenotype, therapy and outcome in 38 Turkish patients with HT1 diagnosed during the last 20 years.
  
  
  RESULTS
  None of the patients was diagnosed on newborn screening. The patients were grouped according to acute, subacute and chronic forms of the disorder. The main clinical manifestations were hepatosplenomegaly, liver and renal tubular dysfunction. Thirty-six patients were treated with nitisinone. The mean duration of nitisinone treatment was 64 months and the mean dosage was 1.2 mg/kg/day. Dietary compliance problems were frequent. Eleven patients had cognitive evaluation (mean total IQ, 84 points). Six patients had living donor liver transplantation despite nitisinone treatment: three due to suspected HCC, two for non-compliance to diet, and one for both, at a median age of 90 months.
  
  
  CONCLUSIONS
  Nitisinone treatment is effective and improves both short- and long-term prognosis of HT1. Early diagnosis on newborn screening is needed because delay in treatment increases the risk of the persistence of hepatic disease and HCC. Interruption of the drug can lead to re-occurrence of hepatocellular damage and neurological crisis. Increased α-fetoprotein and new hypoechoic nodule formation are the warning signs for HCC.
authors.affiliation: Department of Pediatrics, Division of Nutrition and Metabolism, Istanbul University, Istanbul, Turkey.
authors.forename: A Cigdem Aktuglu
authors.initials: AC
authors.lastname: Zeybek
authors.forename: Ertugrul
authors.initials: E
authors.lastname: Kiykim
authors.forename: Erdogan
authors.initials: E
authors.lastname: Soyucen
authors.forename: Serif
authors.initials: S
authors.lastname: Cansever
authors.forename: Suheyla
authors.initials: S
authors.lastname: Altay
authors.forename: Tanyel
authors.initials: T
authors.lastname: Zubarioglu
authors.forename: Tulay
authors.initials: T
authors.lastname: Erkan
authors.forename: Ahmet
authors.initials: A
authors.lastname: Aydin
mesh_terms: D000208:Acute Disease; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003512:Cyclohexanones / Q000627:therapeutic use*; D004035:Diet Therapy; D042241:Early Diagnosis; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006529:Hepatomegaly / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D009579:Nitrobenzoates / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D013163:Splenomegaly / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D014421:Turkey / Q000453:epidemiology; D020176:Tyrosinemias / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy
chemical_list: D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D009579:Nitrobenzoates; C077073:nitisinone
keywords: NTBC; Turkey; hepatocellular carcinoma; liver transplantation; tyrosinemia type 1