Cobalamin (Cbl) C/D deficiency: Clinical, neurophysiological and neuroradiologic findings in 14 cases

The early onset type of cobalamin (Cbl) C/D deficiency is characterised by feeding difficulties, failure to thrive, hypotonia, seizures, microcephaly and developmental delay. It has an unfavourable outcome, often with early d eath and significant neurological impairment in survivors. While clinical a nd biochemical features of Cbl CID deficiency are well known, only a few is olated case reports are available concerning neurophysiological and neuroim aging findings. We carried out clinical, biochemical, neurophysiological an d neuroradiologic investigations in 14 cases with early-onset of the Cbl CI D defect. Mental retardation was identified in most of the cases. A variabl e degree of supratentorial white matter atrophy was detected in 11 cases by MR imaging and tetraventricular hydrocephalus was present in the remaining 3 patients. Waking EEG showed a clear prevalence of epileptiform abnormali ties, possibly related to the high incidence of seizures in these cases. In creased latency of evoked responses and/or prolongation of central conducti on time were the most significant neurophysiological abnormalities. The sel ective white matter involvement, shown both by neuroradiologic and neurophy siological studies, seems to be the most consistent finding of Cbl C/D defi ciency and may be related to a reduced supply of methyl groups, possibly ca used by the dysfunction in the methyl-transfer pathway.