Overview
Progressive myoclonic epilepsy (PME) is a heterogeneous group of epileptic encephalopathies characterized by myoclonus, progressive neurological decline, and often intractable seizures 1.Diagnosis
Clinical Presentation: Intractable epilepsy with myoclonus, cognitive decline, ataxia, and motor weakness 1.
Laboratory Tests: Elevated plasma homocysteine and decreased plasma methionine levels 1.
Genetic Testing: Identification of MTHFR gene variants, including splice site mutations and missense mutations 1.
Enzymatic Activity: Reduced fibroblast MTHFR activity (typically <10% of normal) 1.Management
First-Line Treatments: Folinic acid supplementation 1.
Adjunctive Therapies: Betaine and methionine supplementation 1.Special Populations
Pediatrics: Early recognition and intervention crucial; MTHFR deficiency can present with mild learning disabilities initially 1.Key Recommendations
Evaluate patients with PME for MTHFR deficiency through plasma homocysteine and methionine levels, and genetic testing 1 (Evidence: Moderate).
Initiate folinic acid therapy in confirmed MTHFR deficiency cases to manage biochemical abnormalities 1 (Evidence: Moderate).
Consider adjunctive betaine and methionine supplementation alongside folinic acid for comprehensive metabolic support 1 (Evidence: Weak).References
1 D'Aco KE, Bearden D, Watkins D, Hyland K, Rosenblatt DS, Ficicioglu C. Severe 5,10-methylenetetrahydrofolate reductase deficiency and two MTHFR variants in an adolescent with progressive myoclonic epilepsy. Pediatric neurology 2014. link
2 Ovesen OC, Jensen EK, Bertheussen KJ. Dislocation of extensor tendons of the hand caused by focal myoclonic epilepsy. Journal of hand surgery (Edinburgh, Scotland) 1987. link