Elevated lactate dehydrogenase in a patient with late-infantile GM1-gangliosidosis

Monosialotetrahexosylganglioside (GM1)-gangliosidosis is a neurodegenerative lysosomal storage disorder caused by mutations in the GLB1 gene encoding the lysosomal enzyme β-galactosidase. When β-galactosidase activity is low or absent, β-linked galactose-containing glycoconjugates build up in neuronal tissue. Aspartate aminotransferase (AST) elevation alone has been reported in patients with infantile or type 1 GM1-gangliosidosis. However, serum lactate dehydrogenase (LD) elevation has not been reported. Here, we report the case of a patient with late infantile GM1-gangliosidosis and elevated serum LD levels. The patient showed a developmental delay at the age of 10 months. He gradually showed pyramidal signs, followed by neurodevelopmental regression at 2 years. He experienced febrile seizures at 2 years and developed epilepsy with unremarkable interictal electroencephalogram findings at 3 years. Blood tests revealed continuous elevation of LD and AST levels without elevation of alanine aminotransferase (ALT). Lactic acid and LD levels were elevated in the cerebrospinal fluid. Brain magnetic resonance imaging at 2 years showed non-specific T2-weighted image, diffusion-weighted image, and apparent diffusion coefficient high-intensity on the deep white matter. A lysosomal enzyme activity test revealed a marked decrease in β-galactosidase activity. Genetic analysis revealed a compound heterozygous GLB1 variant, a previously reported pathogenic variant, and a novel variant of unknown significance, which is thought to result in splice loss of the canonical donor site of IVS6 of GLB1 according to in silico analysis. Neurodegenerative lysosomal storage disorders such as GM1-gangliosidosis would be considered in infants with developmental delays, elevated serum LD and AST levels, and normal ALT levels.