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3例糖原贮积症Ⅱ型患儿的临床特点及GAA基因突变分析
Clinical characteristics and GAA gene mutation in children with glycogen storage disease type II:an analysis of 3 cases
糖原贮积症Ⅱ型 （GSDⅡ）是一种主要由酸性α-葡萄糖苷酶 （GAA）基因突变引起的常染色体隐性遗传病，主要累及心脏、骨骼肌等脏器。本文报道3例经GAA基因分析确诊的GSDⅡ患儿的临床特点和基因突变结果，1例为婴儿型，年龄为4个月，患儿表现为体重不增，呼吸困难，肌张力低，ALT、CK升高，心脏彩超示肥厚型心肌病。2例为晚发型，年龄分别为8岁、13岁，晚发型患儿均表现为持续肝酶升高，其中1例患儿伴反复呼吸道感染，肺功能示限制性通气障碍；另1例患儿伴肌酶升高明显，而肌电图正常。外周血GAA基因检查结果显示3例患儿中共检测出6种致病突变，其中c.2738C > T、c.568C > T为未见报道的新突变。外周血GAA基因检测是有效的诊断该疾病的方法。
Glycogen storage disease type Ⅱ (GSD Ⅱ) is an autosomal recessive disorder caused by a deficiency of the lysosomal glycogen-hydrolyzing enzyme acid α-glucosidase (GAA) and can affect multiple systems including the heart and skeletal muscle. The aim of this study was to investigate three children with GSD Ⅱ confirmed by GAA gene analysis and to report their clinical characteristics and gene mutations. One case was classified as infantile-onset GSD Ⅱ, and two cases as late-onset GSD Ⅱ. The infantile-onset patient (aged 4 months) showed no weight increase and had dyspnea, muscle hypotonia, and increased alanine aminotransferase and creatine kinase; echocardiography showed hypertrophic cardiomyopathy. The late-onset patients (aged 8 years and 13 years respectively) showed persistently elevated liver enzymes; one of them had recurrent respiratory tract infection and restrictive ventilation disorder, and the other case showed significantly increased creatase but normal electromyographic findings. Peripheral blood genetic testing for GAA gene showed six pathogenic mutations in the three cases, and the mutations c.2738C > T and c.568C > T had not been reported. Therefore, peripheral blood genetic testing for GAA gene is an effective diagnostic method.
糖原贮积症II型 / 酸性α-葡萄糖苷酶 / 基因突变 / 儿童
Glycogen storage disease type II / Acid-alpha-glucosidase / Gene mutation / Child
[1] Kishnani PS, Howell RR. Pompe disease in infants and children[J]. J Pediatr, 2004, 144(5 Suppl):S35-S43.
[2] Liu Y, Yang Y, Wang B, et al. Infantile Pompe disease:a case report and review of the Chinese literature[J]. Exp Ther Med, 2016, 11(1):235-238.
[3] Kishnani PS, Hwu WL, Mandel H, et al. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease[J]. J Pediatr, 2006, 148(5):671-676.
[4] Chan J, Desai AK, Kazi ZB, et al. The emerging phenotype of late-onset Pompe disease:a systematic literature review[J]. Mol Genet Metab, 2017, 120(3):163-172.
[5] Chu YP, Sheng B, Lau KK, et al. Clinical manifestation of late onset Pompe disease patients in Hong Kong[J]. Neuromuscul Disord, 2016, 26(12):873-879.
[6] Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline[J]. Genet Med, 2006, 8(5):267-288.
[7] Pérez-López J, Selva-O'Callaghan A, Grau-Junyent JM, et al. Delayed diagnosis of late-onset Pompe disease in patients with myopathies of unknown origin and/or hyperCKemia[J]. Mol Genet Metab, 2015, 114(4):580-583.
[8] Lukacs Z, Nieves Cobos P, Wenninger S, et al. Prevalence of Pompe disease in 3,076 patients with hyperCKemia and limb-girdle muscular weakness[J]. Neurology, 2016, 87(3):295-298.
[9] Hermans MM, van Leenen D, Kroos MA, et al. Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type Ⅱ[J]. Hum Mutat, 2004, 23(1):47-56.
[10] 陈素琴, 陈路明, 田秋红, 等. 婴儿肥厚型心肌病一家系GAA基因的突变分析[J]. 中山大学学报(医学科学版), 2014, 35(1):139-143.
[11] Shieh JJ, Lin CY. Identification of a small deletion in one allele of patients with infantile form of glycogen storage disease type Ⅱ[J]. Biochem Biophys Res Commun, 1996, 219(2):322-326.
[12] 单岩东, 王朝东, 张昆南, 等. Ⅱ型糖原累积病的研究进展[J]. 中国临床神经科学, 2007, 15(2):203-207.
[13] Shieh JJ, Lin CY. Frequent mutation in Chinese patients with infantile type of GSD Ⅱ in Taiwan:evidence for a founder effect[J]. Hum Mutat, 1998, 11(4):306-312.
[14] Montalvo AL, Cariati R, Deganuto M, et al. Glycogenosis type Ⅱ:identification and expression of three novel mutations in the acid alpha-glucosidase gene causing the infantile form of the disease[J]. Mol Genet Metab, 2004, 81(3):203-208.
[15] Herzog A, Hartung R, Reuser AJ, et al. A cross-sectional single-centre study on the spectrum of Pompe disease, German patients:molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations[J]. Orphanet J Rare Dis, 2012, 7:35.
[16] Yang CF, Yang CC, Liao HC, et al. Very early treatment for infantile-onset Pompe disease contributes to better outcomes[J]. J Pediatr, 2016, 169:174-180.e1.
[17] Johnson EM, Roberts M, Mozaffar T, et al. Pulmonary function tests (maximum inspiratory pressure, maximum expiratory pressure, vital capacity, forced vital capacity) predict ventilator use in late-onset Pompe disease[J]. Neuromuscul Disord, 2016, 26(2):136-145.
中南大学湘雅三医院新湘雅人才工程（20150312）。
