SEROTONIN DEFICIENCY IN PHENYLKETONURIA EMBRYOPATHY

The development and evolution of PKU can be prevented by prescribing a n appropriate diet at an early age. A systematic neonatal screening ha s been set up in most countries. However, young women suffering from P KU give birth to very severely malformed children (PKU embryopathy: mi crocephaly, mental retardation, hypotrophy, cardiopathy) unless they a gain take up the specific diet, until the PHE level has lowered down t o normal, before the beginning of gestation. The treatment has to be c ontinued at least during the first months of gestation. This managemen t is very unpleasant and sometimes not easily accepted. The mechanism of this embryopathy is still unknown. It is possible that (1) the exce ss of PHE or the presence of abnormal metabolites, or (2) serotonin de ficiency (which is a feature of PKU) could be responsible for the mald evelopment of the embryo. Some authors consider that serontonin has a morphogenetic role in normal embryogenesis. Previously we described an experimental animal model using in vitro culture of rat embryos in hu man PKU sera. Mouse embryos have been subsequently used, since they sh ow a greater sensitivity. Malformations, consisting essentially of neu ral tube defects, were present in almost 100% of the embryos cultured in serum from PKU patients. Using this animal model, we tested the hyp othesis of serotonin deficiency. For this purpose, mouse embryos were cultured in human serum depleted of serotonin. Under these conditions, 100% of the embryos showed oculo-neural malformations characteristic of the experimental embryopathy. These results indicate the importance of serotonin deficiency in the occurrence of PKU embryopathy.