The main reason for the inability to discriminate molecular characteristics of the various GLB1 mutations is the use of synthetic substrates (eg, 4‐MU‐β‐galactoside) for the determination of β‐galactosidase activity, which only allows a rough discrimination between zero residual activities (eg, in infantile GM1‐gangliosidosis), and activities up to 2%‐10% (eg, in late onset GM1‐gangliosidosis and MBD).11 To precisely determine the biochemical characteristics of β‐galactosidase mutants, measurements using natural substrates are needed. The gene discussed is GLB1; the disease is Marchiafava-Bignami disease.