Leukotriene C4 synthesis deficiency: a member of a probably underdiagnosed new group of neurometabolic diseases.

Abstract

Leukotrienes (LTs) are a group of biologically highly active compounds which mainly include the cysteinyl leukotrienes LTC4, LTD4, LTE4 and LTB4. Biosynthesis is limited to a small number of different cells including brain tissue. Besides their well known function in the mediation of inflammation and host defence, cysteinyl LTs have neuromodulatory functions in the brain. Here we describe the recently discovered first two cases with a defect in the synthesis of LTs, LTC4 synthesis deficiency which is characterised by severe muscular hypotonia, psychomotor retardation, failure to thrive, microcephaly, and by the total absence of cysteinyl LTs in body fluids and deficient synthesis of the primary cysteinyl LT, LTC4, in blood cells. We describe the clinical and biochemical findings as well as the pathophysiological aspects of this condition and of further defects suggested in the synthetic pathway of LTs. Moreover, certain disease states which are known to be associated with secondary disturbances of LT degradation are also discussed. Leukotriene C4 synthesis deficiency represents a member of a newly recognised group of neurometabolic disorders which are probably underdiagnosed. Analysis of leukotrienes is recommended in all patients with neurological symptoms who have no apparently obvious metabolic cause.