Tandem mass spectrometric determination of succinylacetone in dried blood spots enables presymptomatic detection in a case of hepatorenal tyrosinaemia

Tyrosinaemia type I, or fumarylacetoacetase deficiency, causes hepatorenal damage by accumulation of fumarylacetoacetate. Patients are generally in good condition at birth, but are at risk of developing serious metabolic crises with liver failure and hepatic coma. An early start of treatment with NTBC and a tyrosine-balanced diet can prevent harm to the patients. The application of tandem mass spectrometry to newborn screening allows for easy determination of tyrosine to detect the presence of hypertyrosinaemia in the neonate, but most patients with tyrosinaemia type I do not present with high tyrosine levels at the time of newborn screening. We report on a 7-week-old girl presenting with acute hepatopathy and severe coagulopathy due to tyrosinaemia type I. The metabolic screening, which was performed by tandem mass spectrometry at the age of 48 h, had revealed normal values for tyrosine and methionine that were well within ranges observed in the general population and equally normal ratios of methionine/tyrosine and tyrosine/serine. In this patient even lowering the cut-off levels for tyrosine and methionine would not have provided better sensitivity. Residual blood spots from the newborn screening filter paper were retrospectively analysed using a specific mass-spectrometric method for the detection of succinylacetone and revealed a 5-fold elevated succinylacetone concentration. This indicates that identification of all newborns with hepatorenal tyrosinaemia is only possible by determination of succinylacetone as part of the newborn screening process.