Hereditary tyrosinemia type 1 from a single center in Egypt: clinical study of 22 cases

World J Pediatr. 2011 Aug;7(3):224-31. doi: 10.1007/s12519-011-0287-3. Epub 2011 Jun 1.

Abstract

Background: Hereditary tyrosinemia type 1 (HT1) is an increasingly recognized inborn error of metabolism among Egyptian children. This study was undertaken to define the presenting clinical, biochemical and imaging features and outcome of 2-(2-motrp-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) therapy and liver transplantation in a cohort of Egyptian children diagnosed with HT1.

Methods: The study was carried out at the Pediatric Hepatology Unit at Cairo University Children's Hospital. HT1 was diagnosed by quantification of succinylacetone (SA) in dry blood spots.

Results: Twenty-two patients were diagnosed with HT1 in a period of 3 years from August 2006 to July 2009. Infants with focal hepatic lesions and hepatomegaly (n=13) were younger at diagnosis than those with rickets (n=5) (median age: 3.25 vs. 10 months; P=0.05). Alpha fetoprotein was highly elevated in all children. Seven children died within a few weeks of diagnosis before therapy was initiated. Ten children were treated with NTBC. The response to NTBC treatment was apparent by a steep drop in serum alpha fetoprotein (AFP) and undetectable SA in urine within 2 months. Three children underwent living donor liver transplantation after treatment with NTBC for 10, 18 and 22 months respectively, despite adequate response to therapy because of financial issues. The explanted livers were all cirrhotic with no dysplasia or malignant transformation.

Conclusions: Focal hepatic lesions are the commonest presentation of HT1 patients and they present at an earlier age than rickets. NTBC is effective but very expensive. Liver transplantation is still considered in HT1 patients.

MeSH terms

  • Child, Preschool
  • Cyclohexanones / therapeutic use
  • Egypt
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Infant
  • Liver Transplantation
  • Male
  • Nitrobenzoates / therapeutic use
  • Tyrosinemias* / diagnosis
  • Tyrosinemias* / therapy

Substances

  • Cyclohexanones
  • Enzyme Inhibitors
  • Nitrobenzoates
  • nitisinone