ATP13A2 gene mutation-related neurodegenerative diseases with myoclonus onset：a case report and literature review

doi:10.16150/j.1671-2870.2026.01.013

Abstract

Abstract:

Mutations in the ATP13A2 gene are associated with various neurodegenerative diseases, including Kufor-Rakeb syndrome (KRS), hereditary spastic paraplegia type 78 (SPG78), neuronal ceroid lipofuscinosis type 12 (CLN12), and amyotrophic lateral sclerosis (ALS). This study reports a case of a rare homozygous mutation in the ATP13A2 gene (Exon12 c.1062G>T: p.Lys354Asn). The patient, a 35-year-old female, initially presented with involuntary tremors in both upper limbs, which were considered posture- and action-induced myoclonus. The symptoms progressively involved both lower limbs, accompanied by bradykinesia, spastic gait in the lower limbs, cognitive impairment, and psychiatric behavioral abnormalities. Electromyography (EMG) revealed paroxysmal EMG discharges in both lower limbs when the patient was in the standing and semi-recumbent positions, with irregular discharge frequencies. Somatosensory evoked potential testing indicated a significant increase in P25 amplitude, suggesting a cortical origin of the myoclonus. The patient was treated with levetiracetam combined with clonazepam to alleviate the myoclonus and levodopa/benserazide combined with pramipexole for parkinsonian symptoms. Significant improvements were observed in myoclonus, muscle rigidity, and bradykinesia, and the patient regained independent ambulation. This mutation site in this patient has not been previously reported in the PubMed database, the Chinese Medical Journal (CMJ) Full-Text Database, Wanfang Database, or the China National Knowledge Infrastructure (CNKI). Amino acid conservation analysis indicated that this site was highly conserved among six vertebrate species, including humans, rats, mice, cattle, chimpanzees, and pigs. According to the genetic mutation classification standards and guidelines of the American College of Medical Genetics and Genomics (ACMGG), this mutation is considered likely pathogenic, exhibiting overlapping phenotypic features of KRS and SPG78. The phenotype of coarse limb myoclonus of cortical origin represents the first reported case associated with this gene, thereby expanding its clinical phenotypic spectrum.

Key words: Myoclonus, ATP13A2 gene, Kufor-Rakeb syndrome, Parkinson's syndrome

CLC Number:

R742
R455

ZHANG Weiwei, HE Xiaoqin, WU Yu, XIAO Qin, TAN Yuyan. ATP13A2 gene mutation-related neurodegenerative diseases with myoclonus onset：a case report and literature review[J]. Journal of Diagnostics Concepts & Practice, 2026, 25(01): 90-95.

Figures/Tables 6

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Table 1

Summary of clinical data of patients with ATP13A2 gene related neurodegenerative diseases

例序	性别	发病年龄	国籍	临床表型	临床症状及体征	基因型	合子性	影像学表现	治疗方案
1^[4]	男	18个月	印度	KRS	运动迟缓、肌强直、核上性凝视麻痹、精神行为障碍	c.1556C >T(p.Thr5191le;c.2440G>A(p.Val814Met)	复合杂合	头颅MRI未见异常	左旋多巴
2^[5]	男	14	毛里求斯	KRS	右侧肢体姿势异常、运动迟缓、核上性凝视麻痹、下面部微小肌阵挛	c.2822delG(p.Ser941Thrfs1X)	纯合	头颅MRI显示双侧尾状核和皮质萎缩，SWI显示双侧尾状核头部、壳核腹侧和黑质铁沉积	左旋多巴、抗胆碱能药物、肉毒素注射
3^[6]	女	青少年	澳大利亚	KRS	运动迟缓、眼睑-舌肌-手指微小肌阵挛	c.3176T>G (p.L1059R)； C.3253delc (p.L1088WfsX4)	复合杂合	肌电图显示与肌阵挛一致的面部肌肉短暂、同步<50 ms肌电爆发	/
3^[7]	女	12	伊朗	KRS及SPG78	运动迟缓、构音障碍、核上性凝视麻痹、癫痫发作、眼睑-下面部-手指微小肌阵挛、下肢痉挛性步态	c.2455C>T（p.Arg819*）	纯合	未见异常	左旋多巴
4^[7]	女	10	伊朗	KRS	运动迟缓、构音障碍、核上性凝视麻痹、头颈部姿势性肌阵挛及双上肢动作性肌阵挛、眼睑-下面部-手指微小肌阵挛、认知障碍、视幻觉	c.2455C>T（p.Arg819*）	纯合	头颅MRI显示弥漫性脑萎缩，额颞区为著	左旋多巴
5^[7]	女	10	波兰	KRS及SPG78	运动迟缓、肌强直吞咽困难、构音障碍、核上性凝视麻痹、口周肌阵挛、下肢痉挛步态、宽基步态、双手意向性震颤、幻听、妄想、认知障碍	c.2209C>T （p.GIn737)；c.2366_2367delTC（p.Leu789Argfs15)	复合杂合	神经传导提示轴突多发性神经病、头颅MRI提示小脑、脑干和额叶皮质萎缩	左旋多巴、奥氮平
6^[8]	女	19	日本	SPG78	下肢痉挛性步态、认知障碍、妄想、癫痫	c.2654C>A (p. Ala885Asp)	纯合	头颅MRI提示胼胝体变薄，额颞叶、尾状核、小脑和脑干萎缩	/
7^[9]	男	30	保加利亚	SPG78	下肢痉挛性步态、认知障碍、小脑性共济失调、浅感觉减退	c.2654C>A (p. Ala885Asp)	纯合	头颅MRI提示小脑和皮质萎缩。神经传导提示运动及感觉神经轴突损害	/
9^[10]	男	24	中国	KRS	震颤、运动迟缓、肌强直、锥体束征、认知障碍	exon28 c.3367C>G（p. Leu1123Val）；exon21 c. 2278G>A（p.Val760Met）	复合杂合	DAT PET/CT显示双侧豆状核尾部多巴胺摄取均减少，左侧明显	左旋多巴
10^[11]	女	51	中国	KRS	静止性震颤、运动迟缓、肌强直	c.3010A>G（p. S1004G）；c.1195+5G>A（splice）	复合杂合	头颅SWI提示双侧黑质燕尾征观察欠清	左旋多巴
11 (本例)	女	26	中国	KRS及SPG78	运动迟缓、下肢痉挛步态、四肢粗大姿势及动作诱发肌阵挛、认知功能障碍、幻觉、妄想。	Exon12 c.1062G>T（p.Lys354Asn）	纯合	头颅MRI及SWI未见异常	左旋多巴、普拉克索、左已拉西坦、氯硝西泮

Table 1

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