Neonatal Diabetes Mellitus due to a Novel Mutation in the GATA6 Gene Accompanying Renal Dysfunction: A Case Report

Objective:

Neonatal diabetes mellitus (NDM) arising from pancreatic agenesis is extremely rare. Mutations in the PDX1, PTF1A, HNF1B, EIF2AK3, RFX6, and GATA6 genes have been shown to result in pancreatic agenesis or hypoplasia. We present a permanent NDM patient with pancreas agenesis and congenital cardiac defects associated with renal dysfunction which has not been previously identified.

Methods:

A male infant was born at 37 weeks gestation by cesarean section because of fetal growth restriction and oligohydramnios. On the first week of life, hyperglycemia was detected. Two months later, the patient was referred to our hospital for glycemic dysregulation, renal and cardiac dysfunction.

Results:

Laboratory investigations revealed a venous glucose level of 256 mg/dL with glycosuria but no ketonuria or acidosis. His serum hemoglobin A1c was 6.6% (normal range, 4.8-5.9%). The patient also had hypoalbuminemia (serum albumin: 2.9 g/dL). Total protein-to-creatinine ratio in spot urine (2.7) was elevated (normal range: <0.7) with normal serum urine and creatinine levels. Abdominal ultrasonography failed to identify any pancreatic tissue. Echocardiography revealed large secundum atrial septal defect, small muscular ventricular septal defect, valvular pulmonary stenosis, and patent ductus arteriosus. Insulin pump therapy including continuous glucose monitoring system was initiated. Analyses of exons 2-7 and exon/intron boundaries of the GATA6 gene were performed and a novel heterozygous nonsense mutation (p.Cys414Ter; c.1242C>A) was identified in the GATA6 gene.

Conclusion:

This report describes a novel heterozygous nonsense GATA6 mutation (p.Cys414Ter) resulting in the clinical picture of congenital heart defects, pancreas agenesis, renal dysfunction (persistent proteinuria), and NDM.