title: Early-onset cobalamin C/D deficiency: epilepsy and electroencephalographic features.
abstract: OBJECTIVE
  To describe epilepsy and EEG findings in the early-onset cobalamin (Cbl) C/D deficiency, an inborn error of intracellular Cbl metabolism characterized by high plasma levels of methylmalonic acid, homocystine, and homocysteine.
  
  
  METHODS
  Type and frequency of seizures were studied in 10 patients (six boys and four girls) who underwent waking and sleep EEG.
  
  
  RESULTS
  Half of patients had seizures in the first year of life (either concurrent with the other symptoms of disease or some months after the onset of disease); seizures occurred after 2 years in the other half of patients. Convulsive status epilepticus was the initial manifestation in three patients. During the follow-up, nine patients had seizures (mainly partial) despite specific treatment for Cbl C/D deficiency and antiepileptic drugs. Focal or multifocal epileptiform abnormalities during waking EEG that increased during sleep EEG were recorded in the majority of patients. Plasma levels of homocystine and homocysteine were constantly higher than normal, despite therapy institution.
  
  
  CONCLUSIONS
  Epilepsy and EEG abnormalities are prominent features in the early-onset type of combined methylmalonic aciduria and homocystinuria due to Cbl C/D deficiency, possibly related to the pathologically and persistently high levels of homocysteine, experimentally proven to induce seizures. Plasma amino acids evaluation and urinary acid organic analysis should be performed in any infant showing seizures associated with feeding difficulties and failure to thrive, at onset during the first year of life, as well as in any child with convulsive status epilepticus and a history of psychomotor developmental delay of unknown origin.
authors.affiliation: III Division of Paediatrics, G. Gaslini Institute, Genova, Italy. roberta.biancheri@tin.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Roberto
authors.initials: R
authors.lastname: Cerone
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Schiaffino
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Caruso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Minniti
authors.forename: Maria Viviana
authors.initials: MV
authors.lastname: Perrone
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortori-Donati
authors.forename: Edvige
authors.initials: E
authors.lastname: Veneselli
mesh_terms: D017668:Age of Onset; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography / Q000706:statistics & numerical data*; D004827:Epilepsy / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006711:Homocystine / Q000097:blood; D006712:Homocystinuria / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood / Q000652:urine*; D012890:Sleep / Q000502:physiology; D014805:Vitamin B 12 / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D014851:Wakefulness / Q000502:physiology
chemical_list: D006710:Homocysteine; D006711:Homocystine; D008764:Methylmalonic Acid; D014805:Vitamin B 12