Purpose To present the clinical presentation and evaluation of a patient with uncontrolled diabetes mellitus (DM), possible MODY-3, and a protuberant abdomen.
Methods Case report.
Results This black female presented with DM at age 12.6 years with a history of polydipsia. Her mother had diabetes “requiring insulin” and the paternal grandmother had probable type 2 diabetes. The patient had obesity (BMI = 32.9 kg/m2), elevated fasting insulin level of 36 μIU/mL (with concomitant glucose of 184 mg/dL), and negative pancreatic antibodies. She was diagnosed with type 2 DM and metformin, 500 mg twice daily, was started. There was sporadic follow-up. The HbA1c ranged from 5.4-6.6% during the first 26 months after diagnosis but had increased to 12.2% six months later. A thiazoladinedione was added but HbA1c remained elevated. Insulin was added. There was poor compliance with all medications and inconsistent adult supervision. She had oligomenorrhea with increased abdominal girth; β-hCG—was negative. CT of the abdomen and small bowel barium study confirmed abdominal situs inversus (right-sided: stomach, small bowel, and multiple splenic masses; left-sided: liver and gallbladder; midline: ascending colon and cecum) and a globular pancreas with a truncated body and tail. Oral glucose tolerance testing (OGTT; 1.75 g/kg to a maximum of 75 g) showed peak glucose and insulin levels of 361 mg/dL and 20.2 μIU/mL, respectively. MODY-3 genetic analysis (Esoterix Laboratory Service, Inc.) demonstrated a novel, heterozygous nucleotide cytosine to adenine substitution at position +20 of intron 1. In addition, she had two other previously described variants in exons 1 and 4 of the hepatocyte nuclear factor 1-α gene, but which are thought not to have clinical significance.
Discussion While certainly measurable, the insulin level during the OGTT seemed inappropriately low for the degree of hyperglycemia, which suggests limited β cell function. Negative pancreatic antibodies mitigate against type 1A diabetes.
Conclusion We present an unusual case of type 2 DM with a novel mutation at +20 of intron 1of the MODY-3 gene associated with abdominal situs inversus, polysplenism, and truncated pancreatic anatomy. While there may not be a causal link, mutations within introns, such as the one we identified in the MODY-3 gene, can lead to alterations in mRNA splicing that affect gene function. Gene product analysis has not yet been performed. Complete MODY-3 analysis on the mother remains pending.