Liver Disease in Transaldolase Deficiency: Molecular Basis, Genotype-Phenotype Relationships, and Transplantation...

Transaldolase deficiency (TALDO-D) is an ultra-rare disorder of the non-oxidative pentose phosphate pathway with prominent liver disease and systemic accumulation of polyols and seven-carbon sugars. We systematically reviewed hepatic manifestations, molecular findings, genotype-phenotype relationships, and liver transplantation (LTx) experience. PubMed/MEDLINE and Europe PMC were searched from inception to 10 August 2026, with citation tracking; supplementary Scopus and Web of Science Core Collection searches were performed on 19 August and 1 September 2026, respectively. Twenty-nine primary clinical reports were included. Individual-patient reconciliation supported 51 genetically/biochemically confirmed patients as the primary analytic set; inclusion of one diagnostically uncertain patient with a homozygous in-frame TALDO1 variant reported as a variant of uncertain significance produced an upper-bound sensitivity set of 52. Seven patients underwent LTx. TALDO1 variants were heterogeneous, and intrafamilial and intragenotypic variability precluded reliable genotype-based prediction. LTx may provide organ-specific rescue for advanced liver disease, but persistent renal, endocrine, hematologic, and metabolic abnormalities require lifelong multisystem surveillance.