cobamamide and Atrophy

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.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Atrophy; Brain; Brain Diseases, Metabolic, Inborn; Child; Child, Preschool; Cobamides; Cytosol; Electroencephalography; Evoked Potentials; Female; Follow-Up Studies; Homocystinuria; Humans; Infant; Intellectual Disability; Magnetic Resonance Imaging; Male; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Seizures; Vitamin B 12; Vitamin B 12 Deficiency

The administration of 2g/kg of di(2-ethylhexyl)-phthalate (DEHP)-induced severe testicular atrophy coincident with the reduction of testicular specific lactate dehydrogenase (LDH-X) activity, zinc, magnesium, and potassium concentrations in rats. Co-administration of DEHP and adenosyl cobalamin (AdoCbl), one of the active vitamin B12s, prevented these testicular specific changes including fluctuations in testicular weight. On the other hand, co-administration of DEHP and methylcobalamin (MeCbl), the other active vitamin B12, did not prevent the testicular atrophy induced by DEHP under the present experimental conditions. In the liver, DEHP administration caused hypertrophy with changes in several metal concentrations and serum biochemical parameters. Co-administration of DEHP and AdoCbl or MeCbl did not prevent these hepatic changes, but aggravated hypolipidemia. The results demonstrated that the preventive effect of AdoCbl was a testicular specific action, and this effect may be stimulated solely by AdoCbl in vitamin B12 groups.

Topics: Animals; Atrophy; Cobamides; Diethylhexyl Phthalate; Hypertrophy; Liver; Male; Rats; Rats, Wistar; Testis