Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent and profound hypoglycemia in infants. There are two distinct histologic forms of CHI, diffuse and focal. The distinction between these forms is important in patients who fail medical therapy since surgical strategies may vary. Focal lesions occur due to paternally inherited recessive mutation in ABCC8 or KCJN11 genes with somatic loss of the maternal 11p15 region (paternal uniparental disomy). Patients with focal CHI can be cured with partial pancreactomy, but a few cases with focal lesion have been reported to have spontaneous resolution.
Case report: Twenty-seven months old male patient has been diagnosed with diazoxide unresponsive CHI in neonatal period in another center. He has been using octreotide treatment since discharge. His parents were consanguineous with no family history of diabetes. On physical examination the patient had microcephaly, bilateral medial strabismus, and neuromotor retardation. His height was 83.5 cm (−1.98 SDS), weight: 10.8 kg (−1.86 SDS). The patient was subjected to genetic analysis for determining long-term therapeutic approach. Mutational analysis revealed paternally inherited two novel mutations of KCJN11 gene (p.L270M and p.E288K). A maternally inherited KCJN11 mutation has not been found and therefore a focal lesion is highly suspected. Since 18-Floro-L-DOPA positron emission tomography (PET) is not available in our country, the focal lesion could not be identified. In the clinical course we observed that the patient tolerated overnight fasting under very low dose octreotide and consider clinical remission. He has been receiving no medications for the last ten months and is still euglycemic.
Conclusion: Genetic analysis is very useful to identify focal CHI in those patients who could be not subjected to 18-Floro-L-DOPA-PET. Although very rare, patients with paternally inherited KCJN11 mutations might response to medical treatment and subsequently clinical remission might be observed.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology