The metabolism of fatty acids in human bietti crystalline dystrophy

PURPOSE. TO investigate the role of abnormal lipid metabolism in Bietti cry stalline dystrophy. METHODS. Cultured human lymphocytes and fibroblasts from patients with Biet ti crystalline dystrophy (BCD) were incubated in the presence of [C-14]18:3 n-3 or [C-14]18:2n-6. Incorporation into the cellular lipid pools and furth er metabolism by desaturation or elongation were monitored by thin-layer ch romatography and HPLC. Results were compared with those in normal control s ubjects and patients with Wolman disease (WD). RESULTS. Pulse-chase experiments with labeled fatty acids in all groups sho wed that, after 1 hour, radioactivity was largely confined to the triacylgl yceride (TG) and choline phosphoglyceride (CPG) pools. However, after sever al hours, radioactivity was transferred from the TG and CPG pools, some goi ng to the serine and ethanolamine phosphoglyceride (SPG and EPG) pools. Fib roblasts from all groups showed direct transfer of fatty acids (FAs) into C PG and EPG. Incorporation of labeled FAs into the EPG pool paralleled exten sive desaturation and elongation of 18:2n-6 to 22:5n-6 and 18:3n-3 to 22:6n -3. Fibroblasts from patients with WD (a lysosomal acid lipase deficiency c haracterized by excessive lipid accumulation), showed higher incorporation of 18:2n-6 into TGs than did normal or BCD fibroblasts. Conversely, fibrobl asts from patients with BCD showed lower conversion of 18:3n-3, but not of 18:2n6, into polyunsaturated FAs (PUFAs) than those of normal subjects or p atients with WD. This was true for total FAs, CPGs, and EPGs. Similar resul ts were found in both fibroblasts and lymphocytes; however, unlike fibrobla sts, lymphocytes from normal subjects showed similar levels of incorporatio n of FAs into EPGs and CPGs. In contrast, incorporation of 18:3n-3 into EPG s was decreased in lymphocytes from patients with BCD. CONCLUSIONS. BCD is characterized by a lower than normal conversion of FA p recursors into n-3 PUFA, whereas there is a higher than normal level of nd and n-3 FAs incorporation into TGs in cells from patients with WD. These fi ndings raise the possibility that abnormal lipid metabolism associated with BCD is the result of deficient lipid binding, elongation, or desaturation in contrast to the lysosomal acid lipase deficiency found in Wolman disease .