Abstract
Treatment and follow-up in Hereditary Tyrosinemia type 1 (HT-1) patients require comprehensive clinical and dietary management, which involves drug therapy with NTBC and the laboratory monitoring of parameters, including NTBC levels, succinylacetone (SA), amino acids, and various biomarkers of liver and kidney function. Good adherence to treatment and optimal adjustment of the NTBC dose, according to clinical manifestations and laboratory parameters, can prevent severe liver complications such as hepatocarcinogenesis (HCC). We analyzed several laboratory parameters for 15 HT-1 patients over one year of follow-up in a cohort that included long-term NTBC-treated patients (more than 20 years), as well as short-term patients (one year). Based on this analysis, we described the overall adherence by our cohort of 70% adherence to drug and dietary treatment. A positive correlation was found between blood and plasma NTBC concentration with a conversion factor of 2.57. Nonetheless, there was no correlation of the NTBC level with SA levels, αFP, liver biomarkers, and amino acids in paired samples analysis. By separating according to the range of the NTBC concentration, we therefore determined the mean concentration of each biochemical marker, for NTBC ranges above 15–25 μmol/L. SA in urine and αFP showed mean levels within controlled parameters in our group of patients. Future studies analyzing a longer follow-up period, as well as SA determination in the blood, are encouraged to confirm the present findings.
Highlights
Published: 13 December 2021Hereditary tyrosinemia type-1 (HT-1) is an autosomal recessive inborn error of metabolism caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (FAH), which affects the degradation pathway for tyrosine (Tyr) and leads to insufficiency in glucogenic metabolites
Treatment is based on the daily administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a herbicide that strongly inhibits the enzymatic activity of 4-hydroxy-phenylpyruvic dioxygenase (4HPPD), the Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
In Chile, there is no NBS for Hereditary Tyrosinemia type 1 (HT-1), 14 of the 15 patients were diagnosed by clinical manifestation; the other was diagnosed as a result of sibling diagnosis 25 days after birth
Summary
Hereditary tyrosinemia type-1 (HT-1) is an autosomal recessive inborn error of metabolism caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (FAH), which affects the degradation pathway for tyrosine (Tyr) and leads to insufficiency in glucogenic metabolites. Increased SA levels are found in biological fluids in affected newborns, and chronic elevation of these metabolites leads to the development of hepatocellular carcinoma (HCC), renal tubulopathy, glomerular disease, heart disease, and neurological problems [3,4]. Diagnosis is crucial to promptly initiate pharmacological treatment and prevent the onset of critical complications. Treatment is based on the daily administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a herbicide that strongly inhibits the enzymatic activity of 4-hydroxy-phenylpyruvic dioxygenase (4HPPD), the Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
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