Dominant activating mutations in GCK gene are known to be the cause of congenital hyperinsulinism (CHI). Patients with GCK mutations can have a wide range of clinical presentations, varying from asymptomatic adult onset hypoglycemia to medically unresponsive severe neonatal onset HI. Overall, 5 of 214 (2.3%) patients diagnosed with HI over the last 10 years in Russia were found to carry pathogenic variants of GCK gene. Only 2 of these 5 patients showed response to high doses of Diazoxide (14.4 and 20 mg/kg/day), whereas others were found to be medically unresponsive. Here we report a severe GCK-HI case which required pancreatectomy. The female patient with normal birth weight and unremarkable neonatal period had her first episode of hypoglycemic seizures at the age of 14 months after weaning off nighttime feeds. At the age of 16 months the girl was admitted to Endocrinology Research Centre (Moscow, Russia), where persistent hyperinsulinemic hypoglycemia was revealed. Interestingly, the patient had normal neurological status. However, the girl had poor response to 20 mg/kg/day Diazoxide and 18 µg/kg/day Octreotide. As the condition deteriorated and the patient got more frequent hypoglycemic episodes followed by drowsiness, stable euglycemia was achieved at glucose infusion rate as high as 19 mg/kg/min. Yet it caused anorexia and dramatic weight gain. A continuous subcutaneous glucagon infusion attempt has failed. Genetic analysis using NGS technology has revealed a mutation in GCK gene NM_000162.4: c.1361_1363dupCGG CI093751 in 11% of reads in the blood sample. Direct sequencing has confirmed the presence of mosaicism. Considering persistent hypoglycemia, high glucose infusion rate and severity of the mutation, the patient underwent near-total pancreatectomy which led to a transient normoglycemia. A few weeks after the surgery the persistent hypoglycemic episodes reoccurred. Low glucose diet with fructose intake and 12 mg/kg/day Diazoxide did not improve the condition. Partial response was achieved on 10 µg/kg/day Octreodite in combination with Nifedepine. Continuous flash glucose monitoring (FreeStyle Libre) appeared quite accurate and helpful in this case. A neurologic examination at the age of 21 months showed normal neurodevelopment with no signs of hypoglycemic brain injury. In summary, near-total pancreatectomy led to some improvement, although did not completely cure the patient. The necessity of near-total pancreatectomy in GCK-HI patients is debatable. Activating mutations of the GCK gene, which is also expressed in the brain, may possibly have some protective effects by keeping the neuronal cells active even during hypoglycemia.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology