In vitro restoration of deficient β-galactosidase activity in liver of patients with Hurler and Hunter disease

Abstract

HUNTER'S and Hurler's syndromes are recessively inherited errors of metabolism, in which accumulation of mucopolysaccharides in tissues is accompanied by skeletal abnormalities and mental retardation. Patients suffering from these diseases show a strikingly reduced activity of β-galactosidase in the liver although this enzyme is not directly involved in the degradation of the glycosaminoglycans that accumulate in the tissues^1–3. This enzyme reduction which is accompanied by an abnormal isoenzyme pattern⁴ can be understood as the result of complex formation between stored mucopolysaccharides and the β-galactosidase enzyme. Indeed artificial mixtures of chondroitin sulphate and liver β-galactosidase show an isoenzyme profile quite analogous to that seen in Hurler's and Hunter's diseases⁵. The isoenzyme abnormality and the reduction in enzyme activity of such an artificial mixture can be neutralised by cetylpyridinium chloride (CPC), a quaternary base which is known to form complexes with mucopolysaccharides⁶. Therefore it seemed possible to restore the β-galactosidase activity of the Hurler and Hunter patients.