title: 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, LTC4-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 LTC4-synthesis deficiency. Our patient most likely represents the second case described so far with this condition. This report provides further evidence that LTC4-synthesis deficiency represents a new neurometabolic disorder.
authors.affiliation: Division of Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Mayatepek
authors.forename: M
authors.initials: M
authors.lastname: Lindner
authors.forename: R
authors.initials: R
authors.lastname: Zelezny
authors.forename: W
authors.initials: W
authors.lastname: Lindner
authors.forename: G
authors.initials: G
authors.lastname: Brandstetter
authors.forename: G F
authors.initials: GF
authors.lastname: Hoffmann
mesh_terms: D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D017997:Leukotriene C4 / Q000096:biosynthesis / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D008661:Metabolism, Inborn Errors / Q000134:cerebrospinal fluid / Q000150:complications / Q000175:diagnosis*; D009123:Muscle Hypotonia / Q000209:etiology; D011596:Psychomotor Disorders / Q000209:etiology
chemical_list: D017997:Leukotriene C4