P2A350: Diagnosis of Congenital Hyperinsulinism After Escherichia Coli Urosepsis in an Infant

Introduction: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children. The presentation may be vague as it mimics the presentation of other pathologies such as sepsis and metabolic diseases. The association between CHI and a predisposition to severe sepsis has not yet been clearly established. We present a case of an infant with persistent hypoglycemia after Escherichia Coli (E. Coli) urosepsis found to have CHI.

Case Description: 3-week-old male ex 35-week infant presented with hypothermia (95.4-degree Fahrenheit), apnea, and respiratory failure. On arrival to pediatric intensive care unit, he was on CPAP but was quickly intubated. Point-of-care (POC) blood glucose was 221 mg/dL but down trended after initial presentation. Blood and urine cultures resulted positive for E. Coli. Cerebral fluid cultures were negative. Patient received cefepime and gentamycin. Patient was eventually transferred to the floor when hemodynamically stable. Blood glucoses were followed, and he continued to have intermittent hypoglycemia (POC < 70 mg/dL) even when antibiotics were completed. When POC and serum venous blood glucose were 47 and 50 mg/dL, respectively, C-peptide was low at 0.4 ng/mL, insulin was low at 0.9 uU/mL, and beta-hydroxybutyrate (BHB) was normal at 0.16 mmol/L. A glucagon challenge after 0.5 milligram of intravenous glucagon showed POC blood glucose of 77, 103, 111, and 128 mg/dL at 1-, 10-, 20-, and 30-minutes post glucagon, respectively. Although, his c-peptide and insulin levels were low at time of critical sample, he had a significant response to glucagon. This in conjunction with normal BHB supported a diagnosis of CHI. He was started on diazoxide and diuril, which were titrated till patient had euglycemia pre-feeds. We have since followed the patient for almost four months and he continues to do well. Whole genome sequencing showed a hemizygous pathogenic variant of BRWD3 c.4006-1G>A.

Discussion: Even though CHI has known monogenic mutations, genetic etiology remains unknown in approximately 40–50% children. Hypoglycemia in our patient was initially suggested to be secondary to urosepsis. Since it was persistent, further investigation was completed and determined it to be secondary to CHI. Currently, the BRWD3 gene is not thought to be related to our patient’s CHI and is thought to be associated with X-linked intellectual developmental disorder-93, macrocephaly, and potentially overgrowth; our patient had macrocephaly since birth. However, it is worth noting that CHI is common in other overgrowth syndromes, such as Beckwith-Wiedemann syndrome, that can be linked to BRWD3 mutation.

Conclusion: Our case highlights the importance of continued blood glucose monitoring even after events such as sepsis, as illness can mask underlying causes for hypoglycemia, such as CHI. It also provides further phenotypic information for a rarely reported BRWD3 gene mutation.