DNA DIAGNOSIS OF X-LINKED ADRENOLEUKODYSTROPHY

The X-linked adrenoleukodystrophy (ALD) gene was identified recently a nd is predicted to encode a 745-amino-acid peroxisomal membrane protei n. Strategies have been designed for the search for mutations in the A LD gene in patients. Several mutations have now been found and it seem s that many different mutations are responsible for ALD. There is no s traightforward correlation between genotype and phenotype since the sa me mutation can cause different ALD phenotypes in the same family. How ever, once a mutation has been found in a family, it can be traced in all at-risk individuals of that family, both post- and prenatally, wit hout the need for very long-chain fatty acid (VLCFA) analysis. Segrega tion analysis with extragenic and intragenic polymorphisms may remain useful in families where mutation analysis is not possible for practic al reasons; VLCFA analysis and measurement of the peroxisomal beta-oxi dation with C-26:0 fatty acid as a substrate will remain the alternati ve. We also briefly discuss the possibilities of DNA diagnosis for oth er peroxisomal disorders.