Clinical and genetic characteristics of 3 children with GM1 gangliosidosis and literature review
10.3760/cma.j.cn113694-20240207-00084
- VernacularTitle:GM1神经节苷脂贮积症患儿临床与遗传学特点及文献复习
- Author:
Xiaoling TIE
1
;
Fengyu CHE
;
Ying YANG
;
Xiaocong CHEN
Author Information
1. 西安市儿童医院康复医学科，西安710003
- Keywords:
Gangliosidosis, GM1;
Child;
beta-Galactosidase;
Mutation, missense;
GLB1 gene
- From:
Chinese Journal of Neurology
2024;57(10):1136-1143
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical, genetic, and bioinformatic characteristics of 3 children diagnosed with GM1 gangliosidosis type Ⅰ, 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.
