Clinical Features, Genetic Spectrum, and Outcome of Hereditary Tyrosinemia Type 1: A Multicenter Study from Southeastern Türkiye

Introduction: Hereditary Tyrosinemia Type 1 (HT1) is a metabolic disorder due to fumarylacetoacetate hydrolase deficiency, which can lead to liver and kidney damage. This study aims to expand our knowledge of the clinical presentation, diagnosis, and outcome of HT1 patients from southeastern Türkiye, a region characterized by high consanguinity rates. Materials and Methods: This retrospective multicenter study included 20 HT1 patients from three metabolic centers in southeastern Türkiye between January 2018 and March 2021. Demographic, clinical, laboratory, and genetic data were retrieved. According to the beginning of the symptoms, patients were divided into acute, subacute, and chronic forms. The statistical analyses consisted of descriptive and inferential methods. Results: The parents of all 20 cases (9F/11M) were consanguineous. The mean diagnostic age was 10.5312.54 months, with an average diagnostic delay of 2.964.42 months. The most common forms were acute HT1 (55%), followed by chronic (25%) and subacute (20%) forms. Common findings were hepatomegaly (40%) and hypotonia/intellectual disability (40%). Tubulopathy was frequent in chronic HT1 (80%). Increased α-fetoprotein levels were found in 60% of the cases at the diagnosis. Hepatocellular carcinoma developed in three patients. Two died of the disease. Genetic studies showed that the most common mutation was IVS6-1G>T (27%). Conclusion: The study highlights the clinical burden and the challenge in managing HT1 in Türkiye, attributed to late diagnosis resulting from absence of newborn screening. Early initiation of NTBC significantly improves the outcome, but long-term follow-up for complications like hepatocellular carcinoma is imperative. Newborn screening programs need to be extended reduce morbidity and mortality associated with HT1.