Infantile epileptic encephalopathy due to cobalamin deficiency?

UH Tacke; KO Schwab; B Fowler; R Korinthenberg

doi:10.1055/s-0031-1273992

Neuropediatrics, Table of Contents

Infantile epileptic encephalopathy due to cobalamin deficiency?

UH Tacke ¹, KO Schwab ², B Fowler ³, R Korinthenberg ¹

¹Zentrum für Kinder- und Jugendmedizin, Neuropädiatrie, Freiburg, Germany
²Zentrum für Kinder- und Jugendmedizin, Endokrinologie, Freiburg, Germany
³Universitäts-Kinderspital beider Basel, Stoffwechselerkrankungen, Basel, Switzerland

Abstract

Objectives: Vitamin B12 deficiency (VBD) in infants mostly results from maternal VBD which can be subclinical and is diagnosed because of the infant's symptoms. We report a case of severe infantile encephalopathy with an unexpectedly favourable course under cobalamin medication.

Case history: A now two year old girl presented with neonatal focal convulsions, increasing in frequency and duration with no response to phenobarbitone.

Diagnostics: Vitamin B12 146,9ng/l (190–631), folic acid 10 (4,6–18.7), holotranscobolamin 17,2pmol/l (>35), MMA in urine 195 (0–10)mmol/mol Crea, homocysteine: 16 (0–13)µmol/l, methionine 14µmol/l (15–35), MCV: 96–99fl, hemoglobin 8,7µg/dl. Thrombocytes and white blood cells were normal and proteinuria was present. EEG showed a constant focal epileptic discharge at the right temporo-mesial site. MRI was normal but cortical dysplasia at the right temporo-mesial site could not be excluded.

Course: There was response to parenteral Vit B12 medication (1mg/day) within one week, but no immediate ceasing of fits so additional of vitamin B6 and folic acid was given and seizures improved and ceased after a few days. She remains on vitamin B12 and phenobarbitol and has no afebrile convulsions. Psychomotor development is normal. Molecular genetics for transcobalamin defects were negative, MRI is normal.

Discussion: 1. The etiology of the epileptic encephalopathy remains unclear. The favourable course under low dose phenobarbitone and cobalamin is very unsusual.

2. Cobalamin deficiency could be due to maternal hyperemesis gravidarum or in accordance with the child's proteinuria due to Imerslund-Gräsbeck syndrome although the neurological symptoms are not typical.

3. The role of pyridoxine and folic acid treatment remains unclear, since this was stopped two years ago and the patient remains free of seizures and the EEG is normal.

Conclusion: There are rare reports on infantile seizures caused by maternal pernicious anaemia responding to cobalamin so that we cannot rule out completely a link between VBD and seizures in our patient.