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.
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.
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DOI：
10.1186/1750-1172-7-35
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发表时间：
2012-06-07
影响因子：
3.7
通讯作者：
Mengel E
中科院分区：
文献类型：
--
作者：
Herzog A;Hartung R;Reuser AJ;Hermanns P;Runz H;Karabul N;Gökce S;Pohlenz J;Kampmann C;Lampe C;Beck M;Mengel E
庞贝氏症（糖原累积病II型，GSD II，酸性α-葡糖苷酶缺乏症，酸性麦芽糖酶缺乏症，OMIM # 232300）是由于酸性α-葡糖苷酶（GAA，酸性麦芽糖酶，EC 3.2.1.20，Swiss-Prot P10253）缺乏而引起的常染色体隐性溶酶体累积病。在整个临床范围内，临床表现以骨骼肌进行性无力为主。此外，典型的婴儿型以肥厚型心肌病为特征。在一项横断面单中心研究中，我们临床评估了3例经典婴儿庞贝氏症患者和39例非经典表现患者，测量了他们的酸性α-葡萄糖苷酶活性并分析了他们的GAA基因。经典的婴儿患者几乎没有残留酶活性，并具有典型的肥厚型心肌病临床病程，直到治疗开始。非经典型患者的疾病表现具有异质性。运动和呼吸功能的下降有很大的差异。发病年龄从出生到成年晚期，与酶活性相关。分子分析显示多达33种不同的突变，其中14种是新的。所有典型的婴儿患者都有两个严重的突变。非经典组中最常见的突变是c。32-13 T > G.在该亚组中，它与较轻的病程相关。疾病表现与GAA突变的性质密切相关，而非经典庞贝氏症的可变进展可能由未知的修饰因素解释。这项研究提供了德国首个关于庞贝氏症临床病程和突变谱的综合数据集。
Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, Swiss-Prot P10253). Clinical manifestations are dominated by progressive weakness of skeletal muscle throughout the clinical spectrum. In addition, the classic infantile form is characterised by hypertrophic cardiomyopathy. In a cross-sectional single-centre study we clinically assessed 3 patients with classic infantile Pompe disease and 39 patients with non-classic presentations, measured their acid alpha-glucosidase activities and analysed their GAA genes. Classic infantile patients had nearly absent residual enzyme activities and a typical clinical course with hypertrophic cardiomyopathy until the beginning of therapy. The disease manifestations in non-classic patients were heterogeneous. There was a broad variability in the decline of locomotive and respiratory function. The age of onset ranged from birth to late adulthood and correlated with enzyme activities. Molecular analysis revealed as many as 33 different mutations, 14 of which are novel. All classic infantile patients had two severe mutations. The most common mutation in the non-classic group was c.-32-13 T > G. It was associated with a milder course in this subgroup. Disease manifestation strongly correlates with the nature of the GAA mutations, while the variable progression in non-classic Pompe disease is likely to be explained by yet unknown modifying factors. This study provides the first comprehensive dataset on the clinical course and the mutational spectrum of Pompe disease in Germany.
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影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
影响因子：
3.9
作者：
Hermans, MMP;van Leenen, D;Reuser, AJJ
通讯作者：
Reuser, AJJ
影响因子：
4.1
作者：
HOEFSLOOT, LH;HOOGEVEENWESTERVELD, M;OOSTRA, BA
通讯作者：
OOSTRA, BA
影响因子：
14.5
作者：
ENGEL, AG
通讯作者：
ENGEL, AG
DOI：
10.1016/0006-291x(91)91906-s
发表时间：
1991-09-16
影响因子：
3.1
作者：
HERMANS, MMP;DEGRAAFF, E;REUSER, AJJ
通讯作者：
REUSER, AJJ