Phenotype, genotype, and outcome of 25 Palestinian patients with hereditary tyrosinemia type 1

Background: Tyrosinemia type 1 (hepatorenal tyrosinemia, HT1) is a rare autosomal recessive inborn
error of tyrosine metabolism caused by deficiency of the last enzyme in the tyrosine catabolic pathway,
fumarylacetoacetate hydrolase (FAH) leading to severe hepatic, renal and peripheral nerve damage if left
untreated. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival.
Material and methods: A retrospective single center study was carried out based on the clinical and
biochemical presentation, therapy and outcome of 25 Palestinian patients with HT1 diagnosed during the
last 25 years.
Results: HT1 is not included in newborn screening program in Palestine. The mean age at diagnosis was 8
months and the main clinical manifestations were coagulopathy, hepatomegaly, splenomegaly and renal
tubular dysfunction. The main biochemical abnormalities were elevated plasma tyrosine, serum transaminases and prothrombin time, and low serum phosphorous with elevated alkaline phosphatase
compatible with hypophosphatemic rickets secondary to renal tubular dysfunction. All patients were
treated with nitisinone. The mean duration of nitisinone treatment was 74 months and the mean dosage
was 0.89 mg/kg/day. None developed HCC or neurological crisis.
Conclusions: Most patients present with liver failure and renal tubular dysfunction. Nitisinone treatment
was effective therapy in all patients and improved both short- and long-term prognosis of HT1. Renal
tubular dysfunction improved in all patients within the first week of starting nitisinone. Early diagnosis is
necessary because delay in the treatment increases the risk of progressive liver failure HCC, progressive
renal disease and neuropathy.
© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).