Epilepsy in children with methylmalonic acidemia: electroclinical features and prognosis

To summarize the electroclinical features and prognosis of epilepsy in children with methylmalonic acidemia (MMA).

The medical records of hospitalized MMA patients associated with epilepsy were retrospectively reviewed. The clinical manifestations, laboratory examination results, and treatment modalities were analyzed.

From 63 pediatric inpatients diagnosed as MMA in Peking University First Hospital from June 1996 to December 2009, 27 children (42.9%) associated with epilepsy were enrolled in this study. These 27 patients were also accompanied with other neurological manifestations including mental retardation or regression (n=22), lethargy (n=10), increased muscle tone (n=8), muscle hypotonia (n=8), recurrent vomiting (n=4), tremor (n=2), ataxia (n=2), and abnormal posture (n=1).The onset age of seizure ranged from 8 days to 11 years. The seizure types included partial seizure (n=21), generalized tonic-clonic seizure (n=5), tonic seizure (n=3), myoclonic seizure (n=3), and epileptic spasms (n=2). Five patients had two or three seizure types. Nine patients (33.3%) had a history of status epilepticus. EEG showed slow background activity in 17 patients, focal or multifocal paroxysmal discharges in 16 patients, generalized paroxysmal discharges in four patients, hypsarrythmia in two patients, and suppression-burst pattern in one patient. Cranial MRI scans showed bilateral cerebral atrophy (n=14), increased T2 signal intensities in white matter (n=12), agenesis of corpus callosum (n=2), bilateral increased T2 signal intensities or necrosis in basal ganglia (n=2), and cerebellar atrophy (n=1). Twenty one patients were MMA combined with homocysteinemia. Seventeen patients were confirmed with cobalamin C disease and one with partial mutase deficiency (mut(-)). Vitamin B12-responsive patients had a better outcome compared with vitamin B12-unresponsive patients.

Epilepsy is a common manifestation of patients with MMA. Partial seizure is more common than other seizure types. Urine organic acid analysis should be performed for children with unknown cause of epilepsy combined with other neurological manifestations, so as to promptly identify the etiology and improve the prognosis.