Pastor-Soler N M, Schertz E M, Rafi M A, de Gala G, Wenger D A
Department of Medicine (Medical Genetics), Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
J Inherit Metab Dis. 1995;18(3):326-32. doi: 10.1007/BF00710424.
Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder resulting from the inability to metabolize sulphatide, an important component of myelin. Although there is significant clinical variability between patients, most have the late-infantile form. It is one of the most common lysosomal disorders involving mental deterioration and is found throughout the world. The great majority of the cases have a deficiency of arylsulphatase A activity. Accurate diagnosis of MLD is complicated by the presence of so-called pseudodeficiency alleles and the need to receive specimens for biochemical testing within 24-48 h of collection. We report the identification of the mutation (a g-to-a transition in the first nucleotide of intron 4) in the arylsulphatase A gene causing late-infantile MLD among the Eskimo population of southern Alaska. As all patients and family members from living and deceased patients had the same mutation, a mutation-based test was developed to identify patients and carriers that can be done on dried blood spots sent via regular mail service. A possible genetic link between this population and the Navajo Indians of the southwestern United States is proposed.
