Transaldolase deficiency – natural disease course towards adulthood

Transaldolase deficiency is a rare metabolic disease caused by pathogenic variants in the TALDO1 gene. Transaldolase plays an important role in the ribose-5-phosphate production, maintaining the NADPH-dependent lipid biosynthesis and cellular redox homeostasis. A small number of patients, predominantly children, have been reported, with a wide range of phenotypic presentations, including liver and kidney disease, involvement of the hematopoietic and endocrine systems, as well as possible early death. We aim to provide further insight into the clinical progression of transaldolase deficiency in adolescence and adulthood. We report on three adult patients with genetically confirmed transaldolase deficiency, including two novel genetic variants in TALDO1. Although the patients have been symptomatic since newborn age, initially with hepatomegaly and cytopenias, they were only diagnosed during adolescence or adulthood. Genetic analysis was performed only at 17, 26, and 32 years, respectively, which, however, did not reveal any genetic variants that would be expected to cause a milder disease course. In adulthood, the dominant clinical features were hypergonadotropic hypogonadism, osteopenia, renal and hepatic involvement. In conclusion, when reporting three new adult cases and comparing them with 47 accessible cases from the literature, our findings suggest that, even if clinical manifestations begin in the neonatal period, the overall phenotype may remain relatively mild, with gradual progression. This means that patients presenting with otherwise unexplained progressive liver disease, kidney dysfunction, cytopenia, and hypergonadotropic hypogonadism should be tested for transaldolase deficiency. We recommend closely monitoring patients with known transaldolase deficiency regarding the above-mentioned problems.