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McKiernan et al describe their experience with early use of nitisinone, previously known as NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione), in infants with hereditary tyrosinaemia type 1 (HT1), diagnosed on neonatal screening, or because of an affected sibling. They report the absence of clinical liver disease, no mortality and improved short-to-medium term neurodevelopment in comparison with other affected children, including their own siblings.1
HT1 is a rare liver-based and kidney-based metabolic disease (estimated UK prevalence 1/100 000), leading to acute liver failure in early infancy, hypophosphatemic rickets, neurological crises, liver cirrhosis and potentially to hepatocellular carcinoma. The mechanism of carcinogenesis is subject to intensive research, but likely related to retention of toxic compounds (maleyl-acetoacetate and fumarylacetoacetate) proximal to metabolic defect in fumarylacetoacetate hydratase enzyme, which catalyses the last step of tyrosine degradation.2 Due to the considerable risk of malignancy this condition represented an almost automatic indication for elective operation in the pioneering days of paediatric liver transplantation (LT). In the early 1990 s, nitisinone was proven to effectively block 4-hydroxyphenylpyruvate dioxygenase activity, thereby significantly inhibiting the production of the toxic metabolites and dramatically reducing requirements for LT.2 However, there are reports showing the development of chronic liver disease and hepatocellular carcinoma in children treated …
Contributors NH has written the first draft while RV has provided additional information and critical comments. Both authors have read and approved the final version.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
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