Km defect in neuraminidase of dysmorphic type sialidosis with and without beta-galactosidase deficiency

Kinetic studies of 4-methylumbelliferyl neuraminidase activity were carried out in cultured skin fibroblasts from patients with various disorders of neuraminidase deficiency. Cell extracts from two patients with dysmorphic type sialidosis of infantile onset, with isolated deficiency of neuraminidase activity, and three patients with dysmorphic type sialidosis of juvenile onset, with combined deficiency of neuraminidase and beta-galactosidase activities, demonstrated 7-12 times higher apparent Km values than those of normal controls (1.0-1.5 mmol/l as compared with 0.12-0.15 mmol/l). The apparent Ki values for N-acetylneuraminic acid and colominic acid were also increased in the dysmorphic type (7-15 and 7-11 times the normal values, respectively). In contrast, in the normomorphic type, normal apparent Km and Ki values were found for 4-methylumbelliferyl neuraminidase activity in fibroblasts from one patient with isolated neuraminidase deficiency and two patients with combined deficiency of neuraminidase and beta-galactosidase. The altered kinetics in the dysmorphic cases indicates a primary defect in neuraminidase with a secondary deficiency of beta-galactosidase in patients with combined deficiency. It is not clear if the primary defect in the normomorphic cases involves a defect in neuraminidase other than a Km defect or if neuraminidase or both neuraminidase and beta-galactosidase deficiencies are secondary to another defect as yet undetermined.