Abstract
This study presented two Chinese adult female patients who were diagnosed with adult-onset Krabbe disease (KD) and reviewed this disease in Chinese patients. Two young female adults in their 20s were enrolled in this study. Clinical data, including symptoms, magnetic resonance imaging (MRI) scanning, and laboratory studies were collected. Sequence alignment and structural modeling were carried out to analyze the pathogenesis of the disease. Both patients were adult-onset and both had a mild clinical course, presented with spastic weakness. The MRI study showed demyelination confined to the corticospinal tracts and parieto-occipital white matter. The β-galactocerebrosidase (GALC) activity was obviously decreased in both patients. Gene test of GALC showed that both patients were compound heterozygotes; proband I was a carrier of p.L634S (c.1901 T > C) and p.I250T (c.749 T > C), while proband II was a carrier of p.L634S (c.1901 T > C) and a new variant of c.283_284del. Molecular analysis revealed the variants may influence the function of GALC. We provided two Chinese adult-onset KD, and the clinical and genetic characteristics of proband II was especially rare due to asymmetric symptoms, spinal cord involvement, and the identification of a new point mutation c.283_284del in the GALC gene. Variant c.749 T > C can present mild syndromes except for severe cases. c.283_284del is a new variant that may occur in adult-onset type.
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All data, models, and code generated or used during the study appear in the submitted article.
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Acknowledgments
We are indebted to the families for their participation in this study.
Funding
The study was funded by the National Key R&D Program of China, Precision Medicine Program, Cohort study on nervous system diseases (2017YFC0907700), the National Natural Science Foundation of China (grant number 81571633), Beijing Health System Clinicians Training Plan (grant number 20143054), and Capital Citizen Health Training Project (No. Z131100006813020).
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Chengyi Zhang analyzed the data and drafted the manuscript. Zheng Liu performed the clinical evaluation and arranged the tests for the probands and their family members. Huiqing Dong made the final diagnosis and reviewed the article. All authors read and approved the final manuscript.
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This study was approved by the Ethics Committee of Xuanwu Hospital of Capital Medical University. Informed consent to participate was obtained from all individual participants included in the study.
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Zhang, C., Liu, Z. & Dong, H. Two Cases of Female Chinese Adult-Onset Krabbe Disease with One Novel Mutation and a Review of Literature. J Mol Neurosci 71, 1185–1192 (2021). https://doi.org/10.1007/s12031-020-01742-1
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DOI: https://doi.org/10.1007/s12031-020-01742-1