Fulminant non‐autoimmune diabetes presenting as fatal diabetic ketoacidosis in a 2‐month‐old infant with genetically confirmed Wolcott–Rallison syndrome

AIMS: Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive monogenic disorder caused by mutations in the EIF2AK3 gene. Characterized by permanent early-onset non-autoimmune diabetes and multisystem dysfunction, it should be strongly suspected in infants presenting under 6 months of age, particularly in consanguineous families. METHODS: A 2-month-old female infant presented to the emergency department with severe respiratory distress, persistent vomiting and dehydration, initially having been evaluated for infantile colic. RESULTS: Laboratory analysis revealed fulminant diabetic ketoacidosis (DKA) (pH 6.85, plasma glucose 40.1 mmol/L, base excess -29 mmol/L). Despite aggressive PICU management, the patient rapidly developed diffuse cerebral oedema, systemic capillary leak, DIC-like coagulopathy with normal transaminases and refractory circulatory shock, leading to death 55 h after admission. Pancreatic autoantibodies were negative, with profoundly suppressed insulin (<0.4 mU/L) and C-peptide levels. Genetic analysis identified a homozygous loss-of-function EIF2AK3 variant, c.1565G>A (p.Trp522*), confirming WRS. CONCLUSION: WRS can present with fulminant DKA and progress to catastrophic multiorgan collapse early in infancy. This case highlights the crucial need to consider monogenic non-autoimmune diabetes in early-infantile DKA and underscores the clinical challenge of distinguishing primary metabolic organ failure from secondary complications of severe DKA and shock. Early molecular diagnosis remains vital for family counselling.