P-230: Long-term survival in Wolcott-Rallison syndrome: a rare case of atypical evolution
E Barbosa de Oliveira Val, A Dantas Costa-Riquetto, A C Santomauro Junior, R Naves Mayrink Barreto Novais, M Gurgel Teles BezerraAbstract
Introduction
Wolcott-Rallison syndrome is a rare autosomal recessive genetic disorder caused by mutations in the EIF2AK3 gene, characterized by neonatal diabetes, hepatic dysfunction, skeletal abnormalities, and growth retardation.
Objectives
To describe the atypical evolution of a patient with WRS.
Methods
This case report is based on a review of medical records from a tertiary hospital, including multidisciplinary follow-up in immunology, nephrology, endocrinology, and pulmonology.
Results
The patient, a 26-year-old male from a consanguineous marriage, developed neonatal diabetes mellitus at 3 months of age, presenting with diabetic ketoacidosis; he has remained on insulin therapy ever since. At 8 years of age, he was diagnosed with secondary immunodeficiency characterized by IgA deficiency and CD4 lymphopenia, which led to recurrent infections, primarily pneumonias. At 12 years of age, systemic arterial hypertension and renal tubular acidosis were identified. Genetic analysis revealed the c.1192C>T (p.Q398X) variant in exon 7 of the EIF2AK3 gene, classified as a nonsense mutation. Notably, unlike most cases reported in the literature—where liver failure is the leading cause of early death, typically occurring in infancy or early childhood—this patient did not develop hepatic insufficiency, enabling exceptional long-term survival into adulthood
Conclusions
WRS exhibits marked clinical heterogeneity, permitting survival into adulthood in rare instances, as illustrated by this 27-year-old proband who has far exceeded the typical life expectancy for the disease, with survival rates are 89.4% at 1 year, 65.5% at 5 years, and 53.1% at 10 years. This is likely attributable to the absence of hepatic failure, early diagnosis, and rigorous multidisciplinary follow-up.This case highlights the marked phenotypic variability of the disease.