# Hereditary tyrosinaemia type 1 in the absence of succinylacetone: 4‐oxo 6‐hydroxyhepanoate (4OHHA), a putative diagnostic biomarker

## TL;DR

This paper identifies a new biomarker for diagnosing a rare metabolic disease when a traditional marker is undetectable.

## Contribution

The study introduces 4-oxo-6-hydroxyheptanoate as a potential diagnostic biomarker for HT1 when succinylacetone is undetectable.

## Key findings

- Three HT1 cases showed atypical biochemistry with undetectable succinylacetone.
- 4-oxo-6-hydroxyheptanoate was identified as a possible alternative biomarker for HT1.
- The findings suggest the need for additional diagnostic markers in HT1 cases.

## Abstract

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.