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Cobalamin (Cbl) C/D deficiency: clinical, neurophysiological and neuroradiologic findings in 14 cases
R Biancheri1, R Cerone, M C Schiaffino
1III Division of Paediatrics, G. Gaslini Institute, Genova, Italy. roberta.biancheri@tin.it
Insights
Early-onset cobalamin C/D deficiency causes severe neurological issues. Neuroimaging and neurophysiology reveal consistent white matter damage, potentially due to methyl group supply problems.
Area of Science:
- Biochemistry
- Neurology
- Genetics
Background:
- Early-onset cobalamin (Cbl) C/D deficiency presents with severe symptoms like hypotonia, seizures, and developmental delay, often leading to poor outcomes.
- While clinical and biochemical aspects are known, neurophysiological and neuroimaging findings in this condition are sparsely reported.
Purpose of the Study:
- To investigate the clinical, biochemical, neurophysiological, and neuroradiologic features of early-onset cobalamin C/D deficiency.
- To identify consistent neurological findings in affected individuals.
Main Methods:
- Clinical, biochemical, neurophysiological, and neuroradiologic assessments were performed on 14 patients with early-onset Cbl C/D deficiency.
- Magnetic Resonance (MR) imaging and Electroencephalography (EEG) were utilized.
Main Results:
- Mental retardation was prevalent. MR imaging showed supratentorial white matter atrophy in 11 cases and tetraventricular hydrocephalus in 3.
- EEG revealed frequent epileptiform abnormalities, correlating with a high incidence of seizures.
- Neurophysiological studies indicated increased latency of evoked responses and prolonged central conduction times.
Conclusions:
- Selective white matter involvement is a consistent finding in early-onset Cbl C/D deficiency, observed through both imaging and neurophysiological studies.
- This white matter damage may stem from a compromised methyl group supply due to methyl-transfer pathway dysfunction.
Abstract:
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 death and significant neurological impairment in survivors. While clinical and biochemical features of Cbl C/D deficiency are well known, only a few isolated case reports are available concerning neurophysiological and neuroimaging findings. We carried out clinical, biochemical, neurophysiological and neuroradiologic investigations in 14 cases with early-onset of the Cbl CID defect. Mental retardation was identified in most of the cases. A variable 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 abnormalities, possibly related to the high incidence of seizures in these cases. Increased latency of evoked responses and/or prolongation of central conduction time were the most significant neurophysiological abnormalities. The selective white matter involvement, shown both by neuroradiologic and neurophysiological studies, seems to be the most consistent finding of Cbl C/D deficiency and may be related to a reduced supply of methyl groups, possibly caused by the dysfunction in the methyl-transfer pathway.