Hypoglycemia in CDG patients due to PMM2 mutations: Follow up on hyperinsulinemic patients.

Shanti Balasubramaniam,Ruqaiah Altassan,Carolyn Ellaway,Pascale De Lonlay,Saadet Mercimek‐Andrews,Eva Morava,Hossein Moravej,David Coman,Peter Witters,Jaak Jaeken,Gregory M Enns

doi:10.1002/jmd2.12085

Abstract

BackgroundPhosphomannomutase 2 deficiency (PMM2‐CDG) is the most common congenital disorder of glycosylation (CDG). Hypoglycemia has been reported in various CDG including PMM2‐CDG. The frequency and etiology of hypoglycemia in PMM2‐CDG are not well studied.MethodsWe conducted a systematic review of the literature on genetically and/or biochemically confirmed PMM2‐CDG patients who developed hypoglycemia. Prospective follow‐up information on the patients who received diazoxide therapy was collected and evaluated.ResultsA total of 165 peer‐reviewed articles reporting on 933 PMM2‐CDG patients were assessed. Hypoglycemia was specifically mentioned only in 23 of these patients (2.5%). Hyperinsulinism was identified in 10 patients (43% of all hypoglycemic patients). Among these 10 patients, seven were successfully treated with diazoxide. However, most patients remained on therapy longer than a year to stay free of hypoglycemia.ConclusionHypoglycemia is a rarely reported finding in patients with PMM2‐CDG. Diazoxide‐responsive hyperinsulinism was found to have a good prognosis on medication in our PMM2‐CDG patients with hypoglycemia. No genotype‐phenotype correlation was observed with respect to hyperinsulinism. A prospective study should be undertaken to explore the hypothesis that hypoglycemia is underdiagnosed in PMM2‐CDG and to evaluate whether hyperinsulinism is always associated with hypoglycemia.

Highlights

Phosphomannomutase 2 deficiency (PMM2-CDG, OMIM number: 212065) is the most common congenital disorder of glycosylation (CDG)
SYNOPSIS Hypoglycemia has rarely been reported in phosphomannomutase 2 deficiency (PMM2-CDG) patients
Previous literature showed that hypoglycemia is a rare manifestation of PMM2-CDG, and that it can be the main presentation of the disease

Summary

| INTRODUCTION

Phosphomannomutase 2 deficiency (PMM2-CDG, OMIM number: 212065) is the most common congenital disorder of glycosylation (CDG). In a few PMM2-CDG patients, hypoglycemia has been reported. Upon reviewing the literature on the occurrence of hypoglycemia, and its possible causes, treatment, and outcome in PMM2-CDG patients, we prospectively followed up on previously reported patients and their outcome. SYNOPSIS Hypoglycemia has rarely been reported in phosphomannomutase 2 deficiency (PMM2-CDG) patients. Hyperinsulinism has been detected in about half of the PMM2-CDG patients with hypoglycemia and responded well to diazoxide. Genetically and/or enzymatically confirmed PMM2-CDG patients who developed hypoglycemia and/or hyperinsulinism were included in this review. In order to find risk factors for hypoglycemia or to figure out relations between hyperinsulinism and other manifestations of the disease, we prospectively collected data on the patients who were earlier reported with hyperinsulinism, including other possible clinical manifestations and outcome of their hyperinsulinism on diazoxide treatment. Patients were evaluated according to the Nijmegen pediatric CDG rating scale.[5]

| METHODS

Findings

| DISCUSSION