Clinical and genetic characteristics of 3 children with GM1 gangliosidosis and literature review
Objective To analyze the clinical,genetic,and bioinformatic characteristics of 3 children diagnosed with GM1 gangliosidosis type 1,and to conduct a literature review.Methods From January 2020 through December 2022,a detailed examination,encompassing whole-exon sequencing and the evaluation of β-galactosidase enzymatic function,was undertaken for 3 pediatric inpatients at Xi'an Children's Hospital.Each child presented with distinct clinical features:recurrent seizures,developmental delays,and hypotonia.Concurrently,computational tools MutaBind2 and PyMOL were employed to prognosticate the potential impact of identified genetic mutations.Results All 3 children experienced severe developmental delay or regression in infancy,accompanied by epilepsy.Serum alkaline phosphatase and aspartate aminotransferase were significantly increased.Furthermore,the serum β-galactosidase activity was 1.59％,3.47％,1.96％,respectively.Brain magnetic resonance imaging revealed poor myelination and X-ray examinations demonstrated beak-like changes in the anterior edge of the lumbar spine.All 3 children carried compound heterozygous variants in the GLB1 gene.The c.148T＞C variant had not been previously reported,while the c.785G＞T,c.1438A＞G and c.304C＞G variants were only present in 1 case.It was predicted that the mutated protein exhibited reduced binding affinity,with an interrupted hydrogen bond or the formation of a significant steric hindrance with the neighboring residues.Combined with the literature evidence,it was hypothesized that the mutations could potentially impact the overall structure and stability of the GLB protein,leading to a decrease in enzyme activity.Conclusions The diagnosis and classification of GM1 ganglioside storage disease need to integrate the clinical features,exome sequencing and β-galactosidase activity assay.Bioinformatics analysis is helpful to predict the effect of mutations on protein structure and function.
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