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• 临床研究 •
ENGLISH ABSTRACT
庞贝病12个家系临床及遗传学分析
付俊
李刚
庞咪
宋佳
张杰文
马明明
作者及单位信息
·
DOI： 10.3760/cma.j.cn115354-20211001-00640
Clinical and genetic features of 12 families with Pompe disease
Fu Jun
Li Gang
Pang Mi
Song Jia
Zhang Jiewen
Ma Mingming
Authors Info & Affiliations
Fu Jun
Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, China
Li Gang
Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, China
Pang Mi
Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, China
Song Jia
Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, China
Zhang Jiewen
Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, China
Ma Mingming
Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, China
·
DOI： 10.3760/cma.j.cn115354-20211001-00640
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摘要

目的探讨庞贝病的临床特征及基因突变特点，并分析酶替代治疗效果。

方法回顾性总结自2017年1月至2021年6月就诊于河南省人民医院神经内科的12个庞贝病家系共14例患者的临床资料及基因检测结果，并对部分患者进行治疗后随访。

结果14例患者中12例为晚发型，起病年龄为1.5~37.0岁(平均15.2岁)，2例为婴儿型；主要表现为双下肢近端为主肌无力，可伴易疲劳和肌痛；8例出现呼吸困难，其中1例以呼吸困难为首发表现；血清肌酸激酶水平为172~1397 IU/L(平均878 IU/L)；6例肌电图呈肌源性损害，4例有肌强直放电；10例用力肺活量下降；5例合并脊柱侧弯；13例酸性α葡萄糖苷酶(GAA)活性下降；8例肌肉病理提示空泡肌病。共检测出 GAA基因17个变异，其中c.2331G>C、c.1622C>T、c.1585T>C和c.1837T>C为4个新的可能致病性变异，c.2238G>C和c.2662G>T变异分别出现在5个和3个家系。1例患者接受酶替代治疗并规律随访，示肌力和肺功能均得到改善，而未进行酶替代治疗的患者肌力和肺功能均下降。

结论庞贝病以骨骼肌无力和呼吸功能障碍为主要表现，可合并脊柱畸形，肌酸激酶轻中度升高，肌电图可发现肌强直放电。 GAA基因c.2238G>C和c.2662G>T为国内热点突变，新发现的4个变异丰富了 GAA基因突变谱系。酶替代治疗可改善患者的运动和呼吸功能。

庞贝病;临床特征;酸性α葡萄糖苷酶基因;酶替代治疗
ABSTRACT

ObjectiveTo investigate the clinical and genetic features of Pompe disease, and analyze the effect of enzyme replacement therapy on it.

MethodsA retrospective study was performed. The clinical data and genetic results of 14 patients with Pompe disease from 12 families, admitted to our hospital from January 2017 to June 2021, were collected. Some patients were followed up after therapies.

ResultsTwelve of the 14 patients were late onset, with onset age ranged from 1.5 to 37.0 years (mean 15.2 years), and the other 2 patients were infantile onset. The predominant manifestations included proximal lower limb weakness, accompanied by easy fatigue and myalgia; 8 patients presented with dyspnea, of which one had dyspnea as initial presentation. Serum creatine kinase ranged from 172 to 1397 IU/L (mean 878 IU/L). Electromyography revealed myogenic pattern in 6 patients and myotonic discharge in 4 patients. Forced vital capacity decreased in 10 patients, and scoliosis was detected in 5 patients; 13 patients had decreased acid-alpha-glucosidase (GAA) activity; muscle pathology indicated vacuolar myopathy in 8 patients. Genetic test revealed 17 variants in GAA gene, among which c.2331G>C, c.1622C>T, c.1585T>C, and c.1837T>C were 4 novel likely pathogenic variants. The c.2238G>C and c.2662G>T were found in 5 and 3 families, respectively. Muscle strength and lung function got improvement in 1 patient who received enzyme replacement therapy and had regular follow-up, while muscle strength and lung function were worsened in those who did not receive enzyme replacement therapy.

ConclusionsPompe disease is characterized by skeletal muscle weakness and pulmonary dysfunction, and may be associated with spinal deformity; creatine kinase is mildly to moderately elevated, and myotonic discharge can be detected. GAA c.2238G>C and c.2662G>T are hotspot mutations in China; the 4 novel variants enrich the GAA mutational spectrum. Enzyme replacement therapy may improve motor and pulmonary function.

Pompe disease;Clinical feature;Acid α-glucosidase gene;Enzyme replacement therapy
Ma Mingming, Email: mocdef.3ab6121nolkcam
Copyright by Chinese Medical Association
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引用本文

付俊,李刚,庞咪,等. 庞贝病12个家系临床及遗传学分析[J]. 中华神经医学杂志,2022,21(04)：379-386.

DOI:10.3760/cma.j.cn115354-20211001-00640

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糖原累积病Ⅱ型也称庞贝病、酸性麦芽糖酶缺乏症，是一种因溶酶体酸性α葡萄糖苷酶(acid α-glucosidase， GAA)基因缺陷所导致的常染色体隐性遗传性罕见病 [ 1 , 2 , 3 ]。根据起病年龄不同，庞贝病可分为婴儿型(≤1岁)和晚发型(>1岁)，婴儿型主要表现为肌张力低下、运动发育迟缓、肝肿大、心肌病等；晚发型主要表现为四肢近端肢体无力，部分患者还会以呼吸功能障碍或脊柱畸形为首发表现，较易误诊漏诊 [ 4 ]。骨骼肌病理活检、GAA活性测定和 GAA基因检测可明确诊断该病 [ 5 ]。酶替代治疗目前已被明确可有效改善庞贝病患者的症状，减缓病情进展 [ 6 ]；但因其价格昂贵，国内仅有少数患者进行了酶替代治疗。本研究现总结河南省人民医院神经内科收治的12个庞贝病家系共14例患者的临床资料及基因检测结果，并报道部分患者酶替代治疗后随访结果，以期进一步提高临床医生对该病的认识。
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