Genetic heterogeneity in human neuraminidase deficiency

Abstract

There is a deficiency of human α-N-acetylneuraminidase in several inherited diseases. In patients with mucolipidosis I (refs 1, 2) and in adults with a variant form without bony abnormalities and mental retardation3,4, both also classified as sialidoses4, it is the only deficient enzyme. In mucolipidosis II (‘I-cell’ disease) neuraminidase is one of many deficient lysosomal hydrolases5–7 and a third manifestation combines deficiency of neuraminidase and β-galactosidase8,9. We have investigated the genetic background of these various neuraminidase deficiencies by somatic cell hybridization and co-cultivation. The principal conclusions from work on mutant fibroblasts, reported here, are that at least three gene mutations are involved and that the combined β-galactosidase/neuraminidase deficiency is likely to be due to defective post-translational modification of these enzymes.