Central nervous involvement is common in PGM1-CDG

Abstract

PGM1, the enzyme responsible for the reversible inter-conversion of glucose-1-P and glucose-6-P, is also involved in glycosylation, leading to a wide range of clinical manifestations, such as congenital malformations, hypoglycemia, hormonal dysregulation, myopathy, hepatopathy, and cardiomyopathy. So far, PGM1 deficiency has not been associated with central nervous system involvement or intellectual disability. Seizures and neurologic involvement in PGM1-CDG were thought to be a consequence of hypoglycemia. We reviewed all reported PGM1 deficient patients for the presence of the central nervous system involvement, their treatment and disease history. We detected 17 patients out of the 41 reported PGM1-CDG cases with significant neurologic involvement. Several of these patients had no severe hypoglycemic episodes, or were adequately treated for hypoglycemia with no recurrent episodes of low blood sugars, while one patient had no reported hypoglycemic episodes. We suggest that neurological symptoms are frequent in PGM1-CDG and could present even in the absence of hypoglycemia. The central nervous system should be assessed early on during the diagnostic process to optimize outcome in patients with PGM1-CDG.

Keywords: CDG; Central nervous system; Developmental delay; Glycosylation; Hypoglycemia; Intellectual disability; Phosphoglucomutase 1; Seizures.