| %600964 | ||||||||
| REFSUM DISEASE WITH INCREASED PIPECOLIC ACIDEMIA; RDPA | ||||||||
| Cytogenetic location: 10pter-p11.2 Genomic coordinates (GRCh37): 10:0 - 38,000,000 (from NCBI) | ||||||||
| Gene Phenotype Relationships | ||||||||
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| Clinical Synopsis | ||||||||
| TEXT | ||||||||
| Tranchant et al. (1993) described 4 patients with adult Refsum disease having, in addition to the usual biochemical features (see 266500), accumulation of L-pipecolic acid, another metabolite (derived from L-lysine) catabolized in peroxisomes. The youngest brother died at age 17 from a rapidly progressing neurologic deterioration suggesting that the patients may suffer from a new peroxisomal disorder intermediate between infantile Refsum disease (266510) and adult Refsum disease. Nadal et al. (1995) referred to this disorder as Refsum disease with increased pipecolic acidemia. They performed genomewide linkage analysis in the family described by Tranchant et al. (1993) and were able to demonstrate linkage with significant lod score values by the combination of 3 independent sources of information: multiple affected sibs, first-degree consanguinity, and biochemical discrimination between healthy heterozygous carriers and noncarriers. The study illustrated the power of a dense map of microsatellite markers combined with classic linkage analysis and homozygosity mapping. They demonstrated a lod score of 3.6 between RDPA and the interval defined by D10S249 and D10S466 on 10p in this single consanguineous family. Since this disorder maps to the same site at the tip of the short arm of chromosome 10 where the gene for phytanoyl-CoA hydroxylase (PHYH; 602026) also maps, and since the PHYH gene is the site of mutations in classic Refsum disease, mutations in that gene should be sought in these cases. | ||||||||
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