The Study on Glycosaminoglycans in the Liver in Patients Affected by Genetic Lysosomal Storage Diseases

Acidic glycosaminoglycans (AGAGs) content, composition and molecular weight distribution were determined in liver from childhood, fetus and patients with genetic lysosomal storage diseases (Hurler syndrome, Hunter syndrome severe form, Morquio syndrome, GM1-gangliosidosis type II and I-cell disease). There was a significant reduction in AGAGs content (as uronic acid) of the childhood liver as compared to the fetal liver. The proportion of chondroitin sulfates was observed to be decreased in the childhood liver, while the proportion of heparan sulfate was markedly increased in the childhood liver. Hyaluronic acid, which was not found in the fetal liver, comparised 7.0% of the total AGAGs in the childhood liver. The AGAGs from the childhood liver were appeared to be a relatively lower sulfate content than those from the fetal liver and, postnatally, there was a decline in the amount of large molecular AGAGs with advancing age. There was a 35 to 50-fold increase in AGAGs content of liver from patients with Hurler and Hunter syndromes. The AGAGs accumulated in the livers consisted mainly of heparan sulfate and dermatan sulfate, and were of a much lower molecular weight than those from childhood liver. The major AGAGs accumulated in the liver from Morquio syndrome was keratan sulfate, which was not found in the liver from childhood, fetus and other patients, and the proportion of chondroitin-6-sulfate was also increased. The content and the composition of AGAGs in the liver from GM1-gangliosidosis and I-cell disease were similar to those of childhood liver. However, a molar ratio of hexose to hexosamine was 7.05 for the liver from GM1-gangliosidosis, and that was 8.47 for the liver from I-cell disease, as compared to 0.46 for the childhood liver, respectively