[P1-171] Whole exome sequencing in rare neurometabolic disease: Late infantile GM1 gangliosidosis
GM1 gangliosidosis is a rare lysosomal storage disorder caused by GLB1 mutations. Because of its ultra-rareness and overlapping symptoms with other neurodegenerative diseases, the diagnosis is sometimes challenging, especially in late infantile form with milder phenotype. We report six cases of late infantile GM1 gangliosidosis in our cohort. This study included 23 patients who had undiagnosed white matter changes in brain MRI. The diagnosis of GM1 gangliosidosis was confirmed based on the GLB1 mutations and/or the deficiency of beta-galactosidase activity.
The first two cases were identified by whole exome sequencing and then the other four patients by the skeletal survey, enzyme study, and direct sequencing of GLB1. All six patients presented with developmental delay or regression during late infancy and later developed epilepsy, mostly generalized tonic seizures. No clinical signs of storage disorders were noted, except skeletal abnormalities. Interestingly AST elevations alone with normal ALT levels were found in all patients. The recurrent mutation, D448V of GLB1 gene, occupied 58.3% of total alleles in our cohort.
Conclusively, diagnosis of late infantile GM1 gangiosodisos is challenge due to its rareness and low awareness. Clinical suspicion and skeletal survey would be very important for diagnosis, integrated with the elevation of AST level. We also highlight the clinical usefulness of whole exome sequencing in undiagnosed ultra-rare pediatric neurodegenerative disease.
The first two cases were identified by whole exome sequencing and then the other four patients by the skeletal survey, enzyme study, and direct sequencing of GLB1. All six patients presented with developmental delay or regression during late infancy and later developed epilepsy, mostly generalized tonic seizures. No clinical signs of storage disorders were noted, except skeletal abnormalities. Interestingly AST elevations alone with normal ALT levels were found in all patients. The recurrent mutation, D448V of GLB1 gene, occupied 58.3% of total alleles in our cohort.
Conclusively, diagnosis of late infantile GM1 gangiosodisos is challenge due to its rareness and low awareness. Clinical suspicion and skeletal survey would be very important for diagnosis, integrated with the elevation of AST level. We also highlight the clinical usefulness of whole exome sequencing in undiagnosed ultra-rare pediatric neurodegenerative disease.