Background: Wolcott- Rallison Syndrome (WRS) is an autosomal recessive disorder due to mutations in the gene coding for pancreatic endoplasmic reticulum eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) that typically presents with neonatal diabetes and bouts of acute liver failure and result in death at a median age of 36 months. We report a unique proinflammatory immunologic phenotype that affects outcome of transplantation.
Case 1: A 2-year-old female, weighing 10.4kg, with WRS, homozygous for mutation in exon 9 of the EIF2AK3 gene, admitted in acute liver failure after having developed a viral respiratory infection. She underwent an en-bloc liver-pancreas transplant (LPTx). She is alive and well 8 years after transplantation.
Case 2: A 3-year-old-boy, with 1 missense variant and 1 frameshift variant in the EIF2AK3 gene presented at 3-years of age with liver failure underwent an emergent whole organ liver transplant. With persistent fever, pronounced elevation in several pro-inflammatory cytokines and CXCL9, bone marrow biopsy demonstrating hemophagocytosis, he was started on dexamethasone, etoposide, Gamifant, and anakinra. He succumbed to his disease after 2-months. Gene sequencing was negative for Hemophagocytic Lymphohistiocytosis HLH).
Case 3: A 13-month-old girl with multiple prior sibling deaths from WRS listed for pre-emptive LPTx, revealed marked elevation in sIL-2R, and CXCL9. With bouts of transaminitis she was started on Ruxolitinib. At 15-months-of-age she received an en-bloc LPTx. She is in her second month post transplant and with normal graft function.
Conclusion: Our small series indicate that immune activation in WRS may put them at high risk for HLH.