Fatty alcohol accumulation in the autosomal recessive form of rhizomelic chondrodysplasia punctata.

[neonatal adrenoleukodystrophy]

Patients with the autosomal recessive form of rhizomelic chondrodysplasia punctata (AR -RCDP ) and other generalized peroxisomal disorders are deficient in the incorporation of fatty alcohol into plasmalogen lipids . To determine whether these patients accumulated fatty alcohol , we measured their plasma fatty alcohol concentrations . Plasma octadecanol levels were elevated in six patients with AR -RCDP but tended to be normal in other generalized peroxisomal disorders such as neonatal adrenoleukodystrophy and Zellweger syndrome . Cultured skin fibroblasts from AR -RCDP patients accumulated six-fold more hexadecanol than normal when cells were incubated in the presence of palmitate but had normal hexadecanol content when palmitate was not present in the culture medium . These cells were profoundly deficient in the incorporation of hexadecanol into ether lipids but oxidized hexadecanol to fatty acid normally . AR -RCDP fibroblasts also showed a two - to seven-fold increase in the rate of hexadecanol synthesis , which was associated with an increase in the activity of acyl-CoA reductase . We conclude that patients with AR -RCDP accumulate fatty alcohol due to its impaired incorporation into ether lipids and a greatly increased rate of fatty alcohol synthesis .