Very long-chain fatty acids in Rett syndrome

Rett syndrome (RS), found exclusively in girls, is characterised by a globa l deceleration of psychomotor development, loss of acquired speech, loss of manual skills and subsequent deceleration of head growth. The cause of thi s syndrome is so far unknown. To date there are no biological markers for R S; clinical diagnostic criteria were proposed by the Rett Syndrome Diagnost ic Criteria Work Group 1988. The first objective of this study was to assay the levels of very long-chain fatty acids (VLCFA), i.e. C22:0, C24:0, C26: 0, by gas chromatography in sera of 30 girls with RS. The VLCFA levels in t he studied group were lower than the reference range for healthy children a nd control group. VLCFA levels were again measured after 2 months of L-carn itine administration in the same groups. VLCFA levels had increased. It is possible that the low VLCFA levels have some relation to the lowered carnit ine levels. It may be that low carnitine levels impede transportation to mi tochondria, thus the oxidation of long-chain fatty acids is inhibited, and compensated to a certain extent by intensified beta-oxidation of VLCFA in t he peroxisomal system. Raising carnitine levels could improve substrate del ivery for mitochondrial beta-oxidation of long-chain fatty acids, thus redu cing the use of VLCFA as substrates for beta-oxidation. We consider VLCFA t o be secondary to the pathogenesis of RS, but the possible abnormalities in their levels may provide an insight into the development of this disease. Conclusion Very long-chain fatty acid and carnitine levels are decreased in Rett syndrome L-Carnitine administration increased very long-chain fatty a cid levels in serum.