Fulminant non‐autoimmune diabetes presenting as fatal diabetic ketoacidosis in a 2‐month‐old infant with genetically confirmed Wolcott–Rallison syndrome
Nihal Akçay, İlyas Bingöl, Demet TosunAbstract
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.