Journal of the Endocrine Society
Oxford University Press
SAT-681 Transient Neonatal Diabetes Mellitus Triggered by EIF2AK3 and PTF1A Mutation
Volume: 4, Issue: Suppl 1
DOI 10.1210/jendso/bvaa046.1603




Background: Neonatal diabetes mellitus (NDM) occurs within the first 6 months of life. Advances in molecular genetics have identified various causatives genes. Mutations in EIF2AK3 causes Wolcott-Rallison syndrome characterized by NDM, multiple epiphyseal dysphasia and growth retardation. PTF1A is associated with the development of pancreas and cerebellum. Both EIF2AK3 and PTF1A mutations are causative genes for permanent NDM with spontaneous and autosomal recessive inheritance. We report a neonate with transient NDM with both EIF2AK3 and PTF1A variants confirmed by Sanger sequencing where each parent found to be a heterozygous carrier of each mutation. Case presentation: A two-day old boy was transferred from a local hospital due to hyperglycemia (blood glucose of 385 mg/dL) and glycosuria. Serum c-peptide (0.06 ng/mL) and insulin (0.64 μU/mL) were low. The patient did not present sings of ketoacidosis and was screened negative for pancreatic autoantibodies. The patient did not have any family history of diabetes. Molecular genetic analysis was performed and continuous infusion of intravenous insulin with pre-prandial bolus was started. Oral sulfonylurea therapy was attempted to prevent adverse neurocognitive outcome however, it showed no response and unable to stabilize blood glucose level. Targeted panel sequencing identified two different novel variants: a heterozygous missense mutation (c.3272G>T) in exon 17 of EIF2AK3 gene and heterozygous missense mutation (c.53C > T) in exon 1 of PTF1A gene; both of which have not been previously reported and were no likely pathogenic variants. The patient’s father confirmed to be heterozygous carriers of the EIF2AK3 mutation while mother being heterozygous carriers of the PTF1A mutation. Blood glucose level gradually began to stabilize with insulin therapy, and upon discharge the patient switched to continuous subcutaneous insulin infusion (pump) with continuous glucose monitoring. Conclusions: NDM caused by in combination of EIF2AK3 and PTF1A gene mutation is a rare condition and could resemble the disease progress of transient form of NDM. Although hyperglycemia might not be an issue of lifelong period, early genetic screening and prompt insulin initiation with consistent glucose monitoring are able to prevent further diabetic complications. In addition, the result of genetic testing in our patient raises the possibility of NDM as polygenic form of diabetes.

Ahn, Lee, Lee, Kim, Kim, Cho, Cho, Jung, and Suh: SAT-681 Transient Neonatal Diabetes Mellitus Triggered by EIF2AK3 and PTF1A Mutation Transient Neonatal Diabetes Mellitus Triggered by EIF2AK3 and PTF1A Mutation&author=Moon Bae Ahn,Yoon Ji Lee,Na Yeong Lee,Seul Ki Kim,Shin Hee Kim,Won Kyoung Cho,Kyoung Soon Cho,Min Ho Jung,Byung Kyu Suh,&keyword=&subject=Diabetes Mellitus and Glucose Metabolism,Type 1 Diabetes Mellitus,