Background: Congenital hyperinsulinism (CHI) is a rare heterogeneous disease. Genetic testing is crucial as identifying the underlying aetiology can guide clinical management.
Objective and hypotheses: We investigated the clinical characteristics and genetics of 20 Ukrainian patients with CHI.
Methods: Routine clinical and laboratory investigations were performed on 20 patients with hypoglycemia and unsuppressed C-peptide and p-insulin, diagnostic for CHI. Patients were sub grouped according to whether the hypoglycemia was persistent (n=12) or transient (n=8). KCNJ11 and ABCC8 were sequenced in all patients. Targeted next generation of all the known CHI genes was undertaken in 2 patients with persistent CHI. In one case features of Beckwith-Wiedemann Syndrome prompted methylation and dosage analysis of chromosome 11p15.5. 18F-DOPA PET-CT was performed on 9 cases (75%) with persistent CHI.
Results: Those with persistent CHI were diagnosed earlier compared to those was transient disease (22.5 days [1,8; 54] vs 89.5 days [1.75; 284] P=0.01) and had a higher birth weight (3845g [3625; 4373] vs 3475g [3205; 3937] P=0.001). There was no difference in gender, blood glucose levels, p-insulin or C-peptide at presentation between the groups. A genetic diagnosis was possible for 12/20 (60%) patients (ABCC8 n=10, KCNJ11 n=1, pUPD 11p15.5 n=1). The pick-up rate was higher for those with persistent versus transient CHI (10/12 (83.3%) vs 2/8 (25%) P=0.004). Of the 9 patients who underwent 18F-DOPA PET-CT scan 5 cases with a paternally inherited KATP channel mutation had a focal lesion, whilst diffuse disease was observed in 2 cases with a compound heterozygous ABCC8 mutation and one case with a dominant ABCC8 mutation. Two patients without a mutation had atypical histology. Eleven patients with persistent CHI (91.6%) were treated with short-acting octreotide and/or diazoxide versus 5 patients with transient CHI (62.5%), P>0.05. Nine (75%) patients with persistent CHI underwent surgery due to poor response to medical therapy. Postoperative complications included transient fasting hyperglycemia (n=1), subclinical exocrine insufficiency (n=1) and a cicatricial hernia (n=1). Hypoglycaemia persisted following surgery in 2 patients (with atypical and diffuse disease). Both are currently treated with long acting release octreotide.
Conclusion: Despite persistent CHI being associated with an earlier age at diagnosis and higher birth weight the overlap in the range of these features between those with persistent and transient CHI means that it is not possible to use clinical characteristics to predict disease duration. Genetic testing should therefore be performed in all individuals with CHI to ensure optimal treatment.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology