Outcome of children with hereditary tyrosinaemia following newborn screening

Abstract

Universal NBS for HT1 should be introduced in the UK.

Nitisinone: a review

“…33 Medium-term followup results of the effect of nitisinone treatment on clinical course of HT1 revealed that none of the patients treated from the neonatal period developed detectable liver disease. 44 In sharp contrast, all late-treated HT1 patients had chronic liver abnormalities before receiving nitisinone and developed cirrhosis, and some developed HCC. 23,44,63,68 Larochelle et al reported that LT was performed in 71% of non-nitisinone treated patients and 26% of late-treated patients.…”

“…35,67 Early treatment has been shown to decrease the risk of HCC. 44,46,56 The earlier the nitisinone treatment is commenced, the lower the risk a patient should develop HCC as the exposure of the liver to the mutagenic effects of FAA and MA is lowered. 33 Medium-term followup results of the effect of nitisinone treatment on clinical course of HT1 revealed that none of the patients treated from the neonatal period developed detectable liver disease.…”

“…The drug was found to be effective not only in preventing the acute life-threatening complications of the disease (eg, acute hepatic failure and neurological crises) but also in reducing the need for LT, improving the survival and the quality of life in HT1 patients, especially when started in the newborn period. 8,33,44 The starting dose is 1-2 mg/ kg BW per day. 44 The initial dose can be titrated down by monitoring nitisinone levels without risking metabolic control as judged from plasma SA levels and SA excretion.…”

“…8,33,44 The starting dose is 1-2 mg/ kg BW per day. 44 The initial dose can be titrated down by monitoring nitisinone levels without risking metabolic control as judged from plasma SA levels and SA excretion. 45,46 A few anecdotal patients were reported who did well under doses lower than 1 mg/kg/day.…”

Clinical Features of 29 Patients with Hereditary Tyrosinemia I in Western Turkey

“…Biochemically, patients typically have hypertyrosinemia and toxic metabolites. Toxic metabolites and their derivates such as fumarylacetoacetate (FAA), maleylacetoacetate, succynylacetoacetate (SA) and SA playa major role in tissue damage with hepatic, renal and neurological findings (2). The FAH gene is mapped in human chromosome 15q (15q23-25) and consists of 14 exons spanning over 35 kb of DNA.…”