Clinical utilization of dried blood spot nitisinone (NTBC) and succinylacetone (SA) concentrations in hereditary tyrosinaemia type 1 - A UK centre experience.

BACKGROUND: Dried blood spot monitoring of nitisinone and succinylacetone in hereditary tyrosinaemia type 1 patients is not widely available in the United Kingdom. Currently, biochemical monitoring utilizes urinary succinylacetone, blood spot tyrosine and phenylalanine monitoring, which can lack in convenience and accuracy, respectively.

METHODS: We report the development of a dried blood spot assay for nitisinone and succinylacetone and analysed retrospective clinical and biochemical data for hereditary tyrosinaemia type 1 patients from a single UK centre.

RESULTS: A total of 13 hereditary tyrosinaemia type 1 patients were evaluated. Eleven presented with liver dysfunction (two with associated renal tubulopathy) and two were detected by early sibling screening. All patients (age 0.03-22 months) were commenced on a tyrosine-/phenylalanine-restricted diet and nitisinone at diagnosis. Ten patients were on twice daily dosing and three 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 dried blood spot samples were analysed; 80% of nitisinone concentrations were between 9.2 and 27  µ mol/L when succinylacetone was <0.3  µ mol/L. Patients on twice daily dosing regimens had significantly higher nitisinone concentration compared with those on once daily dosing ( P  < 0.0001). The median dose required in the twice daily doing group was significantly lower when compared with once daily dosing.

CONCLUSIONS: Dried blood spot monitoring for nitisinone and succinylacetone concentrations in hereditary tyrosinaemia type 1 patients is a rapid and convenient method which allows physicians to individualize treatment plans and observe adherence to treatment.