A Rare Cause of Genetic Liver Disease in Children: Transaldolase Deficiency with a Novel Pathogenic Variant in Two...

Transaldolase deficiency is a rare autosomal recessive disease caused by biallelic mutations in the TALDO1 gene. This disorder is characterized by multisystem involvement, including liver disease. Here, we present 2 siblings with transaldolase deficiency and a novel homozygous mutation in the TALDO1 gene. The index case was presented with hepatosplenomegaly and elevated transaminases in infancy. The 11-year-old sibling, who was diagnosed through family screening, also had chronic liver disease with fibrotic changes, despite initially normal liver function tests. Both patients exhibited additional findings, including dysmorphic facial features, hypergonadotropic hypogonadism, proteinuria, and skeletal anomalies such as scoliosis. Liver biopsies revealed periportal and bridging fibrosis without necroinflammatory activity or malignant transformation. In the second case, a 6 mm T2-hyperintense nodular lesion detected on MRI prompted close monitoring for hepatocellular carcinoma. This report highlights the phenotypic variability of TALDO deficiency, the potential for progressive liver damage in asymptomatic patients, and the importance of liver biopsy and imaging in surveillance. Early diagnosis using genetic testing and family screening facilitates the timely management of complications. Given the multisystem nature of the disorder, multidisciplinary follow-up is essential.