PT - JOURNAL ARTICLE AU - S Gallo AU - D Randi AU - M Bertelli AU - Al Salviati AU - M Pandolfo TI - Late onset MLD with normal nerve conduction associated with two novel missense mutations in the <em>ASA</em> gene AID - 10.1136/jnnp.2003.017400 DP - 2004 Apr 01 TA - Journal of Neurology, Neurosurgery &amp; Psychiatry PG - 655--657 VI - 75 IP - 4 4099 - http://jnnp.bmj.com/content/75/4/655.short 4100 - http://jnnp.bmj.com/content/75/4/655.full SO - J Neurol Neurosurg Psychiatry2004 Apr 01; 75 AB - Metachromatic leukodystrophy (MLD) rarely has its clinical onset in young adults, with a combination of cognitive and behavioural symptoms and peripheral neuropathy. Here we present an exceptional case with very late onset at 42 years of age and no clinical or neurophysiological sign of peripheral neuropathy. Molecular analysis revealed compound heterozygosity for two novel missense mutations affecting conserved residues in the arylsulphatase A (ASA) sulphatase and carboxyterminal domains, resulting in an 89% loss of enzymatic activity. This case indicates that MLD needs to be considered in the differential diagnosis of very late onset white matter diseases, even if not accompanied by peripheral nerve involvement.