Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease resulting in acute liver failure in early infancy, hypophosphataemic rickets, neurological crises, liver cirrhosis and risk of hepatocellular carcinoma later on in life. It is caused by the deficiency of the enzyme fumarylacetoacetate hydrolase which is involved in the terminal step of the catabolic pathway of tyrosine. Diagnosis is made through clinical suspicion supported by biochemical abnormalities that result from accumulation of upstream metabolites. Detection of succinylacetone (SA) in dried blood spot or urine remains pathognomonic, however it is not always detectable. Here we describe three cases of HT1 presenting with atypical biochemistry, where SA was not always detectable, highlighting the importance of an additional disease biomarker, 4-oxo-6-hydroxyheptanoate.
Keywords: 4‐oxo 6‐hydroxyhepanoate; emerging diagnostic biomarker; fumarylacetoacetate hydrolase; succinylacetone; tyrosinaemia type 1.
© 2024 The Author(s). JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.