[Molecular pathology of the hyperglycinemias]

Glycine synthase during postnatal development as well as glycine uptake in rat brain mitochondria have been studied. The effect of propionate and methylmalonate on glycine uptake seems to be responsible for the hyperglycinaemia found in the inborn errors of propionate and methylmalonate metabolism (first described as ketotic hyperglycinaemia). On the other hand, the inhibition by methylmalonate of glycine uptake by synaptosomes from rat spinal cord is reported. Finally, the study of postnatal development of synaptic glycine receptors in normal and hyperglicinemic rats shows that the strychnine binding increases much more rapidly in the hyperglycinemic rats, the receptors being at the 10th day approximately 1.5 times more numerous than in control rats. The increased number of glycine receptors in hyperglycinemic rats could be responsible, at least in part, for the neurological damage in non-ketotic hyperglycinaemia. This is not, however, to deny the possible deleterious effect of a shortage of methylene tetrahydrofolate resulting from the lack of glycine synthase activity.