A Severely Affected Infant with Absence of Cysteinyl Leukotrienes in Cerebrospinal Fluid: Further Evidence that Leukotriene C₄-Synthesis Deficiency is a New Neurometabolic Disorder

Abstract

Leukotrienes are potent oxygenated metabolites derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. They comprise the cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) and LTB₄. The rate limiting step in the formation of cysteinyl leukotrienes is the conversion of LTA₄ to LTC₄ catalyzed by the enzyme LTC₄ synthase. Recently, the first inborn error of leukotriene synthesis, LTC_4-synthesis deficiency, has been identified in a patient with a fatal developmental syndrome. We report on an additional infant presenting with severe muscular hypotonia, symmetrical extension in the lower extremities and psychomotor retardation who died at the age of 6 months. Despite intensive investigations no specific diagnosis could be made. Leukotrienes were subsequently analyzed in the cerebrospinal fluid. Concentrations of LTC₄, LTD₄ and LTE₄ were below the detection limit (< 5 pg/ml) whereas LTB₄ was found to be in the upper normal range. The absence of cysteinyl leukotrienes with normal LTB₄ concentration in cerebrospinal fluid is unique and seems to be pathognomonic for LTC_4-synthesis deficiency. Our patient most likely represents the second case described so far with this condition. This report provides further evidence that LTC_4-synthesis deficiency represents a new neurometabolic disorder.

Key words

Cerebrospinal fluid - Cysteinyl leukotrienes - Leukotriene C_4-synthesis deficiency - Neurometabolic disease