Résumé
Adult Refsum disease (ARD) is a rare autosomal recessive neurologic disorder associated with the accumulation in blood and tissues of phytanic acid, a natural compound of exogenous origin whose catabolism is impaired in patients. We present here genome wide linkage analysis of an atypical Retsum disease family where L-pipecolic acid level in blood was also increased, suggesting that the patients suffer from a new peroxisomal disorder intermediate between ARD and Infantile Retsum Disease (IRD, a peroxisomal deficiency disease). We were able to demonstrate significant linkage (lod score = 3.6) between Refsum Disease with Increased Pipecolic Acidaemia (RDPA) and the interval defined by D10S249 and D10S466 on 10p in this single consan guineous family by combining lod score values obtained from analysis of the multiple affected sibs, haplotype homozygosity and from discrimination between healthy carriers and non carriers based on phytanate oxidase measurements. This Illustrates the power of homozygosity mapping with a dense map of microsatellite markers. A similar strategy will allow testing for homogeneity/heterogeneity between RDPA and ARD or the rare complementation groups of IRD.