ESPE Abstracts

Introduction: A promoter mutation (c.167G>T) in the phosphomannomutase 2 (PMM2) gene, either homozygous or occurring in trans with a PMM2 coding mutation, causes hyperinsulinism (HI) and polycystic kidney disease (PKD) – HIPKD. Organ-specific deficiency of PMM2 leads to the restricted phenotype of HIPKD, without typical clinical features of the Congenital Disorder of Glycosylation Type 1a (CDG1a), which is caused by recessive coding variants in PMM2. To date, there are no reports of inflammatory bowel disease (IBD) and aortopathy in relation to HIPKD.

Objectives: To describe the phenotype of HIPKD due to PMM2 gene variants.

Methods: Retrospective data collection of five patients with HIPKD due to compound heterozygosity for the c.167G>T promoter variant and a missense variant in PMM2, managed in a quaternary HI centre.

Results: HI was diagnosed in all cases by 3.5 years, with two presenting in the neonatal period. HI in all patients responded to diazoxide with or without nifedipine. Two are receiving dual therapy, with nifedipine (range 0.66– 1.66 mg/kg/day) allowing diazoxide dose reduction (range 4.16 – 7.39 mg/kg/day). All patients were diagnosed with PKD by the age of 4 years, with three patients diagnosed in the neonatal period. One patient had bilateral nephrectomies and a renal transplant. Four patients have hepatic cysts and two have hepatic fibrosis. Three patients have been diagnosed with Inflammatory Bowel Disease – Unclassified (IBDU), and demonstrate a distinctive pattern of gastric antral inflammatory involvement with foveolar hyperplasia. Dilatation of the aortic root and ascending aorta were found incidentally in two patients - they remain asymptomatic.

Discussion: In HIPKD, HI may present beyond the neonatal period and show variable severity. HI is responsive to diazoxide and nifedipine. The severity of individual organ involvement varies. Our case series suggests that atypical IBD and aortopathy may be additional features of this condition, although the underlying mechanisms are undefined, but presumably relate to abnormal glycosylation. Abdominal symptoms warrant specialist attention and faecal calprotectin may be considered as a non-invasive screening tool for intestinal inflammation if symptoms are suggestive. Monitoring for aortopathy via echocardiogram should be considered.