Therapeutic Monitoring of Patients With Hereditary Tyrosinemia Type 1—A Belgian Monocentric Experience

Hereditary tyrosinemia type I (HT-1) is a rare metabolic disorder treated by NTBC, requiring careful therapeutic and nutritional monitoring. While follow-up traditionally relies on urinary succinylacetone, plasma NTBC and plasma amino acids, dried blood spot (DBS) methods have introduced alternative monitoring options. However, the optimal biochemical monitoring remains debated. This study evaluated the clinical utility of NTBC measurements compared with established biomarkers in HT-1. In this retrospective single-centre study, we analysed biological data from 12 HT-1 patients treated with NTBC over 6 years. We analysed correlations between NTBC, succinylacetone, δ-aminolevulinic acid (δ-ALA) and alpha-fetoprotein concentrations, and compared tyrosine and phenylalanine levels in DBS and plasma. Succinylacetone suppression in both urine and blood was achieved across a broad range of NTBC concentrations, suggesting that blood succinylacetone is a more reliable marker of metabolic control than NTBC levels. Elevated urinary δ-ALA levels were observed in some samples despite unquantifiable succinylacetone, indicating that succinylacetone may not fully reflect neurological risk. NTBC concentrations showed limited correlation with alpha-fetoprotein, reinforcing the continued need for imaging in hepatocellular carcinoma surveillance. DBS measurement of tyrosine and phenylalanine displayed variable biases relative to plasma, particularly for tyrosine, highlighting the challenges of using DBS for nutritional monitoring. While NTBC remains central in the treatment of HT-1 patients, its blood concentrations offer limited added value for long-term monitoring. Focusing on succinylacetone measurement, along with δ-ALA and alpha-fetoprotein to evaluate neurological and hepatic risks, is recommended. Plasma remains the preferred matrix for amino acids monitoring. Larger multi-centre studies are needed to confirm these findings.