A recessively inherited defect in biosynthesis of cysteine-containing
leukotrienes has been demonstrated in two siblings with severe hypotonia,
developmental retardation, microcephaly, and early death. Laboratory studies
showed extremely low concentrations of several leukotrienes in plasma, urine,
and cerebrospinal fluid and showed defective biosynthesis of the
initial cysteinyl-leukotriene, LTC4. A postulated inherited defect
in LTC4 synthase has not yet been proven by enzyme assay or by demonstrating
mutations in the gene that encodes it. Another possible defect in
leukotriene biosynthesis has been described in a 15-year-old male
with mental retardation, mild motor retardation, deafness, and reduced
excretion of LTE4, the major urine metabolite of leukotrienes. A
possible defect in LTE4 biosynthesis has not been proved.1