Novel Heterozygous Mutations in TALDO1 Gene Causing Transaldolase Deficiency and Early Infantile Liver Failure

Abstract

JPGN Volume 52, N T ransaldolase (TALDO) deficiency (OMIM #606003), a recently recognized new inborn error of the pentose phosphate pathway (PPP), has been reported to date in only 10 patients from 6 families, presenting primarily with liver disease and variable clinical course (1–6). The PPP is a multifunctional pathway that plays a pivotal role in supplying ribose-5-phosphate for nucleic acid biosynthesis and for generation of reducing equivalents, which regulate the cellular redox potential via maintenance of the reduced glutathione (GSH) pool and neutralization of reactive oxygen intermediates (ROIs). TALDO is one of the key enzymes responsible for this neutralization. TALDO deficiency was first described in 2001 (1) and has a broad phenotypic heterogeneity, ranging from fetal hydrops (3) to slowly progressive liver cirrhosis (1). The leading symptoms in the neonatal period in all 10 patients reported were bleeding tendencies with thrombocytopenia, abnormal liver function tests, hepatosplenomegaly, hemolytic anemia, and dysmorphic features (antimongoloid slant, low-set ears, and cutis laxa). Interestingly, mental development and motor development were normal in the majority who were assessed (3 patients died before 6 months of age). The biochemical profile of all of the affected patients is similar: elevated urine erythritol, arabitol, ribitol, sedoheptitol, perseitol, sedoheptulose, mannoheptulose, and sedoheptulose-7P (1,2,7). Measurement of TALDO activity in fibroblasts, lymphoblasts or liver tissue, and sequence analysis of the TALDO1 gene confirm the diagnosis. We report an additional patient with TALDO deficiency with the hope of increasing awareness of this rare disorder that should be rential diagnosis of pediatric liver diseases. We also review the literature on TALDO deficiency.