The Abnormalities of Lysosomal Enzymes in Mucopolysaccharidoses

Authors:
  • FHF. van Hoof
    F. van Hoof
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Abstract
The activity of acid hydrolases on 13 substrates has been measured in the liver of normal human subjects and of 32 patients with various forms of mucopolysaccharidoses. The most important abnormalities may be summarized as follows: In 3 patients, there was a complete absence of α‐fucosidase and an excess of fucose in the mucopolysaccharide fraction. The enzymatic deficiency extended to the brain, lung, kidney and urine. In the liver there was also a large increase in the activity of several acid hydrolases, mostly of the α‐galactosidase and of the β‐xylosidase. In 5 patients with pseudo‐Hurler disease (generalized gangliosidosis), the activity of β‐galactosidase, at pH 3.6 was absent and this defect also extended to other tissues. This enzymatic deficiency explains the known accumulation of galactose‐rich mucopolysaccharides and of galactosyl‐N‐acetylgalactosaminyl N‐acetyl‐neuraminyl)‐galactosylceramide (GM1 ganglioside) in the tissues. Several enzymatic activities were greatly elevated, mostly that of α‐fucosidase, α‐galactosidase and N‐acetyl‐β‐glucosaminidase. In 14 patients with an usual form of Hurler syndrome, the activity of acid β‐galactosidase was markedly reduced and this abnormality extended also to the brain and the derm but not to the kidney, spleen and leucocytes. The N‐acetyl‐β‐hexosaminidases, the β‐glucuronidase and the α‐fucosidase were much more active than normally. In two siblings only, affected by an unusual type of Hurler syndrome, there was a marked elevation of β‐galactosidase. The etiological significance of these findings is discussed and a classification of the mucopolysaccharidoses, based on the activity of the lysosomal enzymes in the liver, is proposed.