Cysteinyl
leukotrienes (LTC(4), LTD(4), LTE(4)) are potent
lipid mediators derived from arachidonate in the
5-lipoxygenase pathway. Recently, the first inborn error of
leukotriene synthesis, LTC(4)-synthesis deficiency, has been identified in association with a fatal developmental syndrome. The absence of
leukotrienes in cerebrospinal fluid was one of the most striking biochemical findings in this disorder. We analysed
leukotrienes in cerebrospinal fluid of patients with a broad spectrum of other well-defined
inborn errors of metabolism, including
glutathione synthetase deficiency (n=2),
Zellweger syndrome (n=3),
mitochondrial disorders (n=8),
fatty acid oxidation defects (n=7), organic acidurias (n=7),
neurotransmitter defects (n=5) and patients with non-specific neurological symptoms, as a reference population (n=120). The concentrations of
leukotrienes were not related to age. Representative percentiles were calculated as reference intervals of each
leukotriene. In all patients with an inborn error of metabolism concentration of cysteinyl
leukotrienes and LTB(4) did not differ from the reference group. Our results indicate that absence of cysteinyl
leukotrienes (<5 pg/ml) in association with normal or increased LTB(4) (50.0-67.3 pg/ml) is pathognomonic for LTC(4)-synthesis deficiency. The unique profile of
leukotrienes in cerebrospinal fluid in this new disorder is primarily related to the defect and represents a new diagnostic approach.