ANNALS EXPRESS: Clinical utilisation of dried blood spot Nitisinone (NTBC) and succinylacetone (SA) concentrations in hereditary tyrosinaemia type 1- a UK centre experience.

Dried blood spot (DBS) monitoring of Nitisinone (NTBC) and succinylacetone (SA) in hereditary tyrosinaemia type 1 (HT1) patients is not widely available in the United Kingdom. Currently biochemical monitoring utilises urinary SA, blood spot tyrosine (Tyr) and phenylalanine (Phe) monitoring which can lack in convenience and accuracy respectively. We report the development of a DBS assay for NTBC and SA and analysed retrospective clinical and biochemical data for HT1 patients from a single UK centre over a 6-year period. A total of 13 HT1 patients were evaluated. Eleven presented with liver dysfunction (2 with associated renal tubulopathy) and 2 were detected by early sibling screening. All patients (age 0.03 - 22 months) were commenced on a Tyr / Phe restricted diet and NTBC at diagnosis. Ten patients were on twice daily dosing and 3 were on single daily dosing at the start of monitoring. One patient from each dosing group swapped between dosing regimens at 20 years of age and 8 months of age respectively. A total of 684 DBS samples were analysed; 80% of NTBC concentrations were between 9.2-27umol/L when SA was <0.3umol/L. Patients on twice daily dosing regimens had significantly higher NTBC concentration compared to those on once daily dosing (p<0.0001). The median dose required in the twice daily doing group was significantly lower when compared to once daily dosing. DBS monitoring for NTBC and SA concentrations in HT1 patients is a rapid and convenient method which allows physicians to individualise treatment plans and observe adherence to treatment.