X-linked adrenomyeloneuropathy associated with 14 novel ALD-gene mutations: no correlation between type of mutation and age of onset

Adrenomyeloneuropathy (AMN) represents a milder form of X-linked adrenoleuk odystrophy (ALD), the most frequent peroxisomal disorder. The disease is ch aracterised by an abnormal accumulation of saturated, very long chain, fatt y acids, because of altered peroxisomal beta-oxidation that concomitantly l eads to demyelination in the central and peripheral nervous systems. ALD sh ows a highly variable phenotypic expression and extensive mutation analysis in ALD patients has failed to establish a genotype-phenotype correlation, even in the presence of the same ALD-gene defect. Therefore, we have looked for a relationship between the molecular lesion and the age of onset in 19 patients with a well-classified clinical course of AMN. The nearly complet e novel spectrum of ALD gene mutations identified has revealed no obvious c orrelation between the type of mutation and age of AMN onset in this small series. However, intrafamiliar concordance could be observed with respect t o the occurrence of adrenocortical insufficiency. This supports the idea of one (or more) additional gene(s) contributing to the phenotypic expression of ALD.