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Journal of Lipid Research, Vol. 42, 1395-1401, September 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa

Correspondence to: Dennis R. Hoffman, To whom correspondence should be addressed., dhoffman{at}retinafoundation.org (E-mail)

Many patients with X-linked retinitis pigmentosa (XLRP) have lower than normal blood levels of the long-chain polyunsaturated 3 fatty acid docosahexaenoic acid (DHA; 22:63). This clinical trial was designed to test whether down-regulation of DHA biosynthesis might be responsible for these reduced DHA levels. DHA biosynthesis was assessed in five severely affected patients with XLRP and in five age-matched controls by quantifying conversion of [U-¹³C]-linolenic acid (-LNA) to [¹³C]DHA. Following oral administration of [U-¹³C]-LNA, blood samples were collected at designated intervals for 21 days and isotopic enrichment of all 3 fatty acids was determined by gas chromatography/mass spectroscopy. Activity of each metabolic step in the conversion of -LNA to DHA was determined by comparison of the ratios of the integrated concentration of ¹³C-product to ¹³C-precursor in plasma total lipid fractions. The ratio of [¹³C]DHA to [¹³C]18:33 (the entire pathway) and that of [¹³C]20:53 to [¹³C]20:43 (⁵-desaturase) were significantly lower in patients versus controls (P = 0.03 and 0.05, respectively). The estimated biosynthetic rates of [¹³C]20:53, [¹³C]22:53, [¹³C]24:53, [¹³C]24:63, and [¹³C]22:63 were significantly lower in XLRP patients (42%, 43%, 31%, 18%, and 32% of control values, respectively; P < 0.04), supporting down-regulation of ⁵-desaturase in XLRP. The disappearance of ¹³C-labeled fatty acids from plasma was not greater in XLRP patients compared with controls, suggesting that XLRP was not associated with increased rates of fatty acid oxidation or other routes of catabolism.

Thus, despite individual variation among both patients and controls, the data are consistent with a lower rate of ⁵-desaturation, suggesting that decreased biosynthesis of DHA may contribute to lower blood levels of DHA in patients with XLRP. — Hoffman, D. R., J. C. DeMar, W. C. Heird, D. G. Birch, and R. E. Anderson. Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa. J. Lipid Res. 2001. 42: 1395;–1401.

Supplementary key words: omega-3 fatty acids, retinal degeneration, delta-5 desaturase, stable isotopes, lipid metabolism, linolenic acid

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