Evaluation of serum NEAT1 and MALAT1 expression as diagnostic biomarkers in tyrosinemia, a rare metabolic disorder

OBJECTIVE: Tyrosinemia is a rare autosomal recessive inborn error of metabolism caused by a deficiency of fumarylacetoacetate hydrolase (FAH). This leads to the accumulation of toxic metabolites, resulting in progressive liver and kidney damage. This study aimed to evaluate the serum levels of the long non-coding RNAs NEAT1 and MALAT1 in children with tyrosinemia and assess their potential as diagnostic biomarkers. METHODS: This cross-sectional study included 11 children with tyrosinemia, randomly selected from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), and 26 healthy controls. RNA was extracted from serum samples, and the expression levels of NEAT1 and MALAT1 were quantified using quantitative real-time PCR. RESULTS: Serum NEAT1 expression was significantly upregulated in children with tyrosinemia compared to healthy controls (p = 0.011). In contrast, MALAT1 expression showed a non-significant increasing trend. Correlation analysis revealed a positive association between NEAT1 expression and AST and ALP levels, whereas MALAT1 was inversely correlated with INR in the tyrosinemia group. Receiver operating characteristic (ROC) curve analysis demonstrated that NEAT1 has strong diagnostic potential, with an area under the curve (AUC) of 0.945, 100% sensitivity, and 80% specificity at an optimal cut-off value of 1.126. MALAT1 showed poor diagnostic performance. CONCLUSIONS: Our findings suggest that serum NEAT1 represents a promising, non-invasive biomarker for tyrosinemia. In contrast, MALAT1 does not appear to be a useful diagnostic marker for this condition. CLINICAL TRIAL NUMBER: Not applicable.