INTRODUCTION: Objective: Phosphomannomutase 2 deficiency (PMM2-CDG) is a disorder of protein N-glycosylation with a wide clinical spectrum. Hypoglycemia is rarely reported in PMM2-CDG. In this study, we evaluated cause, treatment options and outcomes in cases with hypoglycemia in the course of PMM2-CDG.
METHODS: Methods: Clinical records of patients followed with PMM2-CDG within last two decades were reviewed. Medical data of patients with hypoglycemia were evaluated in more detail. Demographic and clinical findings, organ involvements as well as laboratory investigations at time of hypoglycemia were recorded. Time of first attack of hypoglycemia, cause, treatment modalities, duration of hypoglycemia (permanent/transient), duration of treatment as well as outcome were also recorded. Other cases with PMM2-CDG and hypoglycemia from literature are also reviewed in order to elucidate characteristics as well as pathophysiology of hypoglycemia.
RESULTS: Results: Nine patients with PMM2-CDG were included, and hypoglycemia was present in three cases. All three had hyperinsulinism as the cause of hypoglycemia. In the first two cases reported here, serum insulin level at time of hypoglycemia was elevated, and glucose response was exaggerated during glucagon test favoring hyperinsulinism. However, in the third case, serum insulin level at time of hypoglycemia was not so high, however hypoglycemia responded well to diazoxide. Hyperinsulinism was permanent in two of these three cases. No genotype-phenotype correlation was observed with respect to hyperinsulinism.
DISCUSSION AND CONCLUSION: Conclusion: Main cause of hypoglycemia in PMM2-CDG seems to be hyperinsulinism. Although insulin levels at time of hypoglycemia may not be very high, hypoglycemia in patients with PMM2 respond well to diazoxide.