Evidence map›Paper›PMID 42087242›Full record

ArticleActa neuropathologica communications2026

Adult-onset Sandhoff disease presenting with a motor neuron disease phenotype: clinical and mechanistic insights from patient-derived models.

Yao Tang, Didi Shan, Hongxu Wang, Xinbo Ji, Yichang Jiao, Jianing Li, Zexin Zhan, Shuangwu Liu, Xiaohan Sun, Pengfei Lin and 6 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Yao TangDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Didi ShanDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Hongxu WangDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Xinbo JiDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Yichang JiaoDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Jianing LiDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Zexin ZhanDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Shuangwu LiuDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Xiaohan SunDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Pengfei LinDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Jingwen XuDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Dongdong WangDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Xiulian SunDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Chuanzhu YanDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China.
Yuying ZhaoDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China. zyy72@126.com.
Fuchen LiuDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Disease, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong, 250012, Jinan, China. fuchen.liu@email.sdu.edu.cn.

Funding

Key R&D Program of Shandong Province No. 2025CXPT133Natural Science Foundation of Shandong Province ZR2023MH180Qilu Young Scholarship of Shandong University 20201125
6 · The paper itself

Abstract

Sandhoff disease (SD) is a subtype of GM2 gangliosidosis caused by pathogenic variants in Hexosaminidase B (HEXB). It most frequently presents in infancy or early childhood, whereas adult-onset disease is rare and remains incompletely characterized. Here, we describe an adult-onset case of SD presenting as motor neuron disease and provide clinical and mechanistic insights using patient-derived models. The patient was a 34-year-old man with compound heterozygous HEXB variants (c.1598G > A, p.Arg533His and c.1645G > A, p.Gly549Arg) who developed progressive lower limb weakness. Muscle biopsy demonstrated neurogenic changes consistent with denervation, and sural nerve biopsy revealed mild peripheral neuropathy. Nerve conduction studies and electromyography showed widespread neurogenic changes with mildly reduced sensory nerve action potential amplitudes, and leukocyte β-hexosaminidase activity was decreased. To investigate disease mechanisms, we generated induced pluripotent stem cells (iPSCs) from the patient and an isogenic CRISPR-Cas9-corrected control (ISO), and differentiated both lines into motor neurons (MNs). In the SD patient (SDHF)-derived MNs, we observed lysosomal expansion, increased apoptosis, reduced neuronal network excitability, and dysregulated lipidomic profiles. These phenotypes were attenuated in MNs derived from the ISO line, with multiple measures shifting toward those of control (CTL) MNs. Collectively, our findings expand the clinical spectrum of adult-onset SD and support an association between HEXB deficiency and the vulnerability of MNs, while underscoring the value of patient-derived iPSC models for mechanistic studies of lateonset SD.

Indexed as

Motor Neuron DiseaseSandhoff DiseaseAdultbeta-Hexosaminidase beta ChainHumansInduced Pluripotent Stem CellsMaleMotor NeuronsNerve Conduction StudiesPhenotypebeta-Hexosaminidase beta ChainHEXB protein, humanCRISPR/Cas9GM2 gangliosidosisiPSCsLipidomicsMotor neuronSandhoff disease

Identifiers

PMID42087242
PMCPMC13321429

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.