Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #112868
Title: ASSESSMENT OF DOCOSAHEXAENOIC ACID (DHA) BIOSYNTHESIS IN PATIENTS WITH X-LINKED RETINITIS PIGMENTOSA (XLRP)

Author
item HOFFMAN, DENNIS - RETINA FOUNDAT OF THE SW
item DEMAR, JAMES - CNRC/BAYLOR COL OF MED

Submitted to: Investigative Ophthalmology and Visual Science
Publication Type: Abstract Only
Publication Acceptance Date: 2/22/2000
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: XLRP is the most severe form of genetically inherited retinitis pigmentosa. Many XLRP patients have lower than normal blood levels of long-chain polyunsaturated Omega3 fatty acid, DHA. To test the hypothesis that down regulation of hepatic DHA biosynthesis is a causative factor of reduced DHA levels in XLRP, DHA biosynthesis was assessed by quantifying conversion of the stable-isotopically labeled precursor, alpha-linolenic acid, to DHA in controls and patients with XLRP. Five patients with severe visual impairment and 5 age-matched controls were provided low-Omega3 fat diets to stabilize Omega3 fatty acid intake. After a medical exam subjects were admitted to the hospital and given an oral bolus of 0.5 g 13C-ALA followed by blood sampling at 1, 1.5, 2, 3, 4, 6, 8, 12, 18 & 24hr and out-patient venipunctures at 2, 3, 4, 5, 7, 10, 14, 21, 28, & 35 days. 13C-enrichment of plasma Omega3 fatty acids was determined by gas chromatography/mass spectrometry and data expressed as peak and total area under the curve for % enrichment as well as % dose. Rates of biosynthesis were defined as the slopes determined by linear regression of initial 13C-enrichment for each intermediate. Compared to controls, patients with XLRP had higher 13C- enrichment of Omega3 fatty acids prior to Delta5 desaturase whereas enrichment of those fatty acids following the Delta5 desaturase step was lower. In addition to a delay in 13C peak enrichment into DHA, patients with XLRP had reduced biosynthetic rates for 13%, 31%, 21% & 40% of controls, respectively. Considerable individual variation was seen among subjects. Nevertheless, the data are consistent with a lower rate of Delta5 desaturation in patients with XLRP. Thus, decreased biosynthesis of DHA may contribute to the lower DHA blood levels in patients with XLRP.