Neurochemical abnormality in I-cell disease: chemical analysis and a possible importance of beta-galactosidase deficiency.

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Abstract—Sphingolipid composition in both gray and white matter of a patient with I‐cell disease was normal except for the higher proportion.of GMI‐ganglioside in gray and white matter. In the patient's liver and kidney there was a significant accumulation of ceramide dihexoside and ceramide trihexoside and of sulphatide in kidney. Non‐lipid hexosamine and sialic acid concentration in brain was increased 1.2‐1.5 times above normal. Recovery of myelin from I‐cell's white matter was 80‐100%, suggesting that demyelination, if present, is minimal. Myelin lipid and myelin specific glycoprotein patterns were normal. Except for β‐galactosidase activity the activity of other brain lysosomal enzymes were within the normal range. This finding was similar to that of Hurler's syndrome. Only β‐galactosidase activity was reduced to less than 10% of normal in the patient's brain. To examine the possible metabolic significance of β‐galactosidase deficiency in I‐cell disease the physical characteristics of this enzyme, isolated from tissues from I‐cell, Hurler and control patients, were compared using isoelectric focusing, Con A‐Sepharose and Sephadex G‐150 chromatography. The isoelectric point and the binding affinity of I‐cell β‐galactosidase with Con A‐Sepharose was comparable to normal. However, the isoenzyme patterns of brain and liver I‐cell β‐galactosidase with Sephadex G‐150 gel filtration revealed decreased acid β‐galactosidase. Effects of the addition of sodium chloride on each fraction of β‐galactosidase isoenzymes isolated from I‐cell tissues were markedly different from controls, whereas the pH optimum of these enzymes were similar to normal. These enzyme characteristics in I‐cell tissues were different from normal and Hurler's syndrome. These findings suggest that β‐galactosidase deficiency in I‐cell disease is a more specific phenomenon rather than secondary inhibition as found in the mucopolysaccharidoses and thus may have an important role for the pathogenesis of brain damage and disease occurrence.