Nitisinone ( Orfadin ) has transformed the management of hereditary tyrosinaemia type 1 ( HT1 ). However, the risk of developing hepatocellular carcinoma is related to the age at which treatment is commenced. Little data on the outcome of children treated pre-emptively exist.
The purpose of a study was to describe the outcome of children with HT1 treated with Nitisinone following selective newborn screening ( NBS ) and to compare their outcome with index siblings who had presented clinically.
12 children with HT1 were detected by newborn screening. Seven children were screened for HT1 because of an affected sibling ( n=5 ). Four children were detected due to raised tyrosine concentrations on routine newborn screening and one child was born in a country with universal newborn screening for HT1.
Nitisinone was commenced at 4 ( 1-52 ) days old. 6 children had an initial coagulopathy which resolved after 4 ( 1-7 ) days treatment.
Currently at median age 8.5 ( 3-12.5 ) years all are clinically normal, with normal liver function tests and imaging. Those of school age are in normal classes but four have reported learning difficulties.
Five index siblings presented clinically with acute liver failure ( 4 ) and chronic liver disease ( 1 ) at median 4 ( 1.5-17 ) months. One died of liver failure prior to Nitisinone's availability.
Four were treated with Nitisinone; one failed to respond and underwent liver transplantation and three responded.
One responder died from complications of prematurity and the remaining two have compensated liver disease.
In conclusion, children with HT1 treated with Nitisinone following newborn screening have an excellent outcome. ( Xagena )
McKiernan PJ et al, Arch Dis Child 2015; Epub ahead of print