Case Report: RAS-associated autoimmune leukoproliferative disorder presenting with early-onset liver failure in a 9-month-old Chinese girl

Abstract

RAS-associated autoimmune leukoproliferative disorder (RALD) is a rare, nonmalignant lymphoproliferative disorder characterized by splenomegaly, autoimmune cytopenia, monocytosis, and somatic RAS pathway mutations. Severe hepatic failure is an uncommon manifestation. Here, we report a critically ill infant with a diagnosis of RALD who presented with fulminant liver failure. A 9-month-old girl presented with recurrent infections, lymphadenopathy, massive hepatosplenomegaly, cytopenia, coagulopathy, and early-onset liver failure. Disseminated Talaromyces marneffei infection was confirmed by two sets of peripheral blood cultures. Whole-exome sequencing (WES) identified a heterozygous KRAS c.351A>C (p.Lys117Asn, K117N) variant located in the GTP-binding domain. The heterozygous state and clinical context are consistent with a somatic mutation in a subset of hematopoietic cells, rather than a germline variant. The patient died two days after admission despite antibiotics and maximal supportive care, including plasma exchange and intravenous immunoglobulin. This case illustrates that RALD-associated immune dysregulation served as the underlying root cause, on the basis of which a disseminated opportunistic infection developed as the direct cause of the fatal deterioration, revealing a potential link between oncogenic RAS signaling and innate immune dysregulation. It underscores the urgency of early genetic screening in infants with unexplained hepatitis and systemic inflammation, while advocating for novel therapeutic strategies targeting RAS/MAPK pathways.