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Lafora disease is a rare and fatal form of progressive myoclonic epilepsy with onset during early adolescence. The disease is caused by mutations in EPM2A, encoding laforin, or EPM2B, encoding malin. Both proteins have functions that affect glycogen metabolism, including glycogen dephosphorylation by laforin and ubiquitination of enzymes involved in glycogen metabolism by malin. Lack of function of laforin or malin results in the accumulation of polyglucosan that forms Lafora bodies in the central nervous system and other tissues. Enzyme replacement therapy through intravenous administration of alglucosidase alfa (Myozyme®) has shown beneficial effects removing polyglucosan aggregates in Pompe disease. We evaluated the effectiveness of intracerebroventricular administration of alglucosidase alfa in the Epm2a -/- knock-out and Epm2a R240X knock-in mouse models of Lafora disease. Seven days after a single intracerebroventricular injection of alglucosidase alfa in 12-month-old Epm2a -/- and Epm2a R240X mice, the number of Lafora bodies was not reduced. Additionally, a prolonged infusion of alglucosidase alfa for 2 or 4 weeks in 6- and 9-month-old Epm2a -/- mice did not result in a reduction in the number of LBs or the amount of glycogen in the brain. These findings hold particular significance in guiding a rational approach to the utilization of novel therapies in Lafora disease., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare genetic disorder caused by pathogenic variants in SLC2A1, resulting in impaired glucose uptake through the blood-brain barrier. Our objective is to analyze the frequency of GLUT1-DS in patients with absences with atypical features. Sequencing analysis and detection of copy number variation of the SLC2A1 gene was carried out in patients with atypical absences including: early-onset absence, intellectual disability, additional seizure types, refractory epilepsy, associated movement disorders, as well as those who have first-degree relatives with absence epilepsy or atypical EEG ictal discharges. Of the 43 patients analyzed, pathogenic variations were found in 2 (4.6%). Six atypical characteristics were found in these 2 patients. The greater the number of atypical characteristics presenting in patients with absence seizures, the more likely they have a SLC2A1 mutation. Although GLUT1-DS is an infrequent cause of absence epilepsy, recognizing this disorder is important, since initiation of a ketogenic diet can reduce the frequency of seizures, the severity of the movement disorder, and also improve the quality of life of the patients and their families., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A benign prognosis has been claimed in benign familial infantile seizures (BFIS). However, few studies have assessed the long-term evolution of these patients. The objective of this study is to describe atypical courses and presentations in BFIS families with mutations in PRRT2 gene. We studied clinically affected individuals from five BFIS Spanish families. We found mutations in PRRT2 in all 5 families. A non-BFIS phenotype or an atypical BFIS course was found in 9/25 (36%) patients harbouring a PRRT2 mutation. Atypical features included neonatal onset, mild hemiparesis, learning difficulties or mental retardation, and recurrent seizures during adulthood. We also report a novel PRRT2 mutation (c.121_122delGT). In BFIS families an atypical phenotype was present in a high percentage of the patients. These findings expand the clinical spectrum of PRRT2 mutations including non-benign epileptic phenotypes., (Copyright © 2014 Elsevier B.V. All rights reserved.)