The mucopolysaccharidoses

Abstract

The article reviews the classification, pathogenesis, laboratory diagnosis, enzyme deficiencies, prenatal diagnosis, and attempts at treatment of the genetic mucopolysaccharidoses. These are classified into six types, with subtypes: Hurler syndrome, Scheie syndrome, and Hurler Scheie combination; Hunter syndrome, severe and mild; Sanfilippo syndrome, A and B; Morquio syndrome; Maroteaux Lamy syndrome, classic and mild form; and β glucuronidase deficiency. The pathological features stem from intracellular accumulation of glycosaminoglycan (GAG) in a number of body tissues. Laboratory diagnosis centers on abnormal urinary excretion of GAGs which is always demonstrable. In patients and heterozygotes, fibroblasts show metachromasia but this makes the diagnosting situation confusing because metachromasia is present in many other metabolic disorders. It is clear that the mucopolysaccharidoses are storage disorders resulting from absence of lysosomal degradative enzymes which have now been identified. The elucidation of the enzyme defects has made possible prenatal diagnosis in many cases but enzyme assays cannot as yet be used to full advantage. Attempts have been made to introduce the missing enzymes by infusion of whole blood, plasma, or leucocytes but long range results have been disappointing, probably because the enzymes are not recognized by the lysosomes and uptake is insufficient. It is suggested that preparation of enzymes with an uptake marker may permit targeting of the enzymes to lysosomes of the relevant levels. (Myrianthopoulos - Bethesda, Md.)