INFECTION-TRIGGERED RECURRENT ACUTE LIVER FAILURE IN CHILDHOOD: IDENTIFICATION OF CONCURRENT NBAS AND SCYL1 VARIANTS BY WHOLE-EXOME SEQUENCING
SSIEM 2026 ANNUAL SYMPOSIUM: NEXT GENERATİON METABOLİC MEDICINE, Helsinki, Finlandiya, 25 - 28 Ağustos 2026, ss.139-140, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: Helsinki
- Basıldığı Ülke: Finlandiya
- Sayfa Sayıları: ss.139-140
- Dokuz Eylül Üniversitesi Adresli: Evet
Özet
IntroductionRecurrent acute liver failure (RALF) in childhood is a rarecondition associated with significant morbidity and mortality.In recent years, defects in vesicular trafficking have been im-plicated in infection-triggered episodes of acute liver failure.Variants in the NBAS gene are associated with Infantile LiverFailure Syndrome type 2, whereas SCYL1 gene variants arelinked to CALFAN syndrome, characterized by cholestasis,acute liver failure, and neurodegeneration.In this study, we present a patient with recurrent episodesof acute liver failure triggered by febrile infections, in whomNBAS and SCYL1 gene variants were identified throughwhole-exome sequencing.Case PresentationA seven-year-old boy was evaluated due to recurrent epi-sodes of vomiting and marked transaminase elevation duringupper respiratory tract infections. The first episode occurred at age 3, followed by two similar episodes in subsequentyears. During the episodes, AST levels rose to up to 1400 IU/Land ALT levels to up to 860 IU/L, with the INR reaching 1.7.Between episodes, liver enzymes and coagulation parameterswere within normal limits. Extensive laboratory investigationsfor inherited metabolic diseases, infectious, and autoimmuneetiologies revealed no abnormalities. Abdominal ultraso-nography and MR cholangiopancreatography showed nostructural abnormalities, and no abnormalities were detect-ed on craniospinal MRI. Whole exome sequencing identifieda homozygous frameshift variant in the SCYL1 gene and ahomozygous missense variant in the NBAS gene. Segregationanalysis showed heterozygous carrier status in both parentsand the unaffected sibling. After the diagnosis, the patientwas assessed early during a febrile episode. He was hospital-ized and received intravenous hydration. During follow-up,as liver function tests increased and coagulation parametersdeteriorated, N-acetylcysteine therapy was started, and earlyimprovement was observed with treatment.ConclusionVariants in NBAS and SCYL1 genes, which are involved invesicular trafficking and Golgi–endoplasmic reticulum retro-grade transport pathways, can lead to hepatocellular stressand injury, resulting in infection-triggered episodes of acuteliver failure. This case highlights the importance of consider-ing vesicular trafficking disorders in the differential diagnosisof pediatric patients with RALF associated with infections.Early genetic diagnosis is crucial for appropriate clinical fol-low-up, management of acute episodes, and genetic counsel-ing of the family.