ESPE Abstracts

Background: Wolcott-Rallison syndrome is a rare autosomal recessive condition. It is characterized by neonatal or early-onset, non-autoimmune insulin-dependent diabetes, spondyloepiphyseal dysplasia, renal or hepatic failure and growth retardation.

Objective: We are reporting a novel homozygous pathogenic mutation in the EIF2AK3 c.1277T>A p. (Leu426*) in a Pakistani child who presented with neonatal diabetes, liver failure, and difficulty in walking.

Case presentation: A 5-month-old boy, born to consanguineous parents, presented to the department of Pediatric Endocrinology and Diabetes, University of Child Health Sciences, The Children's Hospital, Lahore, Pakistan with concern of polyuria, failure to thrive since birth and difficulty in breathing for 2 days. His birth weight was 3.2 kg. He had two healthy siblings. There was a history of one elder brother diagnosed with neonatal diabetes at the age of 3 months, who had a history of liver failure and died at the age of 1.5 years. At presentation, he was found to have persistent hyperglycemia with severe metabolic acidosis and ketonemia. He was started to manage as diabetic ketoacidosis (DKA), and his glycated haemoglobin (HbA1c) was 11% and his C peptide was 0.06 nmol/L, which confirmed the diagnosis of neonatal diabetes. Once stable, discharged on a basal bolus insulin regimen. He had two episodes of acute liver failure at the age of 18 months and 5 years, both of which were managed conservatively. At the age of 6 years, he presented with concern about his short stature and difficulty walking. A skeletal survey was done, which revealed epiphyseal dysplasia. Currently, he is 6.5 years old, with a height of 86 cm (-6.3 SD) and a weight of 11 kg (-4.5 SD). He has distinctive facial features such as frontal bossing, a broad wrist, and kyphosis. The rest of the systemic examination is unremarkable. His latest HbA1c is 8.2%, and he has a normal bone profile (calcium, phosphate, and alkaline phosphatase), thyroid profile, liver function test, and renal function test. An ultrasound of the abdomen revealed no organomegaly. His whole exome sequencing (WES) revealed that he is carrying a novel homozygous pathogenic mutation in the EIF2AK3 c.1277T>A p. (Leu426*), confirming the diagnosis of Wolcott-Rallison syndrome (WRS). The parents were given detailed information about the disease's prognosis and future antenatal screening.

Conclusion: Wolcott-Rallison syndrome is the most common cause of permanent neonatal diabetes mellitus in consanguineous families. EIF2AK3 should be suspected in patients with neonatal diabetes and recurrent hepatic failure.

Keywords: Neonatal diabetes, Liver Failure, Wolcott Rallison Syndrome.