Early-onset cobalamin C/D deficiency: epilepsy and electroencephalographic features.
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.
Biancheri
Roberta
R
III Division of Paediatrics, G. Gaslini Institute, Genova, Italy. roberta.biancheri@tin.it
Cerone
Roberto
R
Rossi
Andrea
A
Schiaffino
Maria Cristina
MC
Caruso
Ubaldo
U
Minniti
Giuseppe
G
Perrone
Maria Viviana
MV
Tortori-Donati
Paolo
P
Veneselli
Edvige
E
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
D006710:Homocysteine; D006711:Homocystine; D008764:Methylmalonic Acid; D014805:Vitamin B 12