AJP Rep. 2026 Sep 18;16(3):e195-e199. doi: 10.1055/a-2946-5351. eCollection 2026 Jul.
ABSTRACT
Objective The objective of this study is to describe the prenatal sonographic and neonatal features of two siblings with lethal transaldolase deficiency and highlight its phenotypic overlap with gestational alloimmune liver disease (GALD). Study Design This is a retrospective review of consecutive pregnancies in a single family, analyzing sequential prenatal ultrasound surveillance, maternal therapeutic interventions, neonatal clinical course, and postmortem trio exome sequencing. Results Both siblings exhibited severe early-onset fetal growth restriction, echogenic bowel, neonatal hemochromatosis, and hypertrophic cardiomyopathy. Because the clinical presentation during the first pregnancy closely mimicked GALD, the second pregnancy was treated empirically with intravenous immunoglobulin (IVIG), which proved entirely ineffective. Subsequent exome sequencing revealed compound heterozygous variants in the TALDO1 gene, including a novel pathogenic variant (p.Arg239Cys). These findings demonstrate that the hepatic pathology in transaldolase deficiency is a primary metabolic process rather than an antibody-mediated alloimmune process. Conclusion Transaldolase deficiency should be considered in the differential diagnosis for fetuses presenting with unexplained severe growth restriction accompanied by echogenic bowel or hepatic echogenicities or in neonates with fulminant liver failure, particularly when associated with cardiomyopathy. This case highlights the value of performing prenatal exome sequencing prior to initiating targeted therapies like IVIG. Establishing a definitive genetic diagnosis prevents the utilization of futile, resource-intensive treatments, optimizing patient care and prognostic counseling.
PMID:42762033 | PMC:PMC13588688 | DOI:10.1055/a-2946-5351