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目的分析幼年起病伴骨骼肌损害的女性Fabry病病例及其家系的临床特点、骨骼肌组织病理及遗传学特性。方法搜集1例女性Fabry病病例的临床资料,并调查对应家系成员;对该病例及其父亲行肌肉活检组织病理检查;测定该病例及其父亲外周血白细胞α-半乳糖苷酶A(GLA)活性,提取外周血DNA,对其GLA基因的7个外显子及其邻近区域进行分段聚合酶链反应扩增及测序分析。结果 (1)该病例为13岁女性,6年前出现发作性双足疼痛,后渐出现不易耐受疲劳;其父自幼无汗,20岁左右出现发作性双足疼痛,后相继出现心肌梗死和脑梗死;另其家系中还有3名男性、5名女性有类似症状;(2)该病例肌肉活检组织病理检查发现肌膜下、肌间质、肌间神经束内有团块状或颗粒样过碘酸希夫染色阳性物质沉积,其父肌肉活检组织病理检查未见明显异常;(3)该病例GLA酶活性轻度下降,其父则显著降低;(4)该病例及其父亲GLA基因检测显示Exon 6 c.837G>C(p.Q279H)错义突变,为已知致病突变。结论女性Fabry病患者亦可早期发病,发作性肢端疼痛和肢体乏力、易疲劳等骨骼肌受累症状可以为主要临床表现。不明原因的心脑血管病患者需排除Fabry病的可能。
Objective To analyze the clinical features, skeletal muscle histopathology and genetics of female Fabry disease and its pedigree from juvenile onset skeletal muscle injury. Methods The clinical data of one female Fabry disease were collected and the corresponding members of the pedigree were investigated. The muscle biopsies of the cases and their fathers were examined by histopathology. The levels of α-galactosidase A (GLA) The DNA of peripheral blood was extracted and the 7 exons of GLA gene and their adjacent regions were amplified by polymerase chain reaction and sequenced. Results (1) The case was a 13-year-old female who developed paroxysmal bipolar pain six years ago and became less resistant to fatigue after her graduation. Her father had no sweat at the age of 20 and had episodic bipolar pain after about 20 years of age, Infarction and cerebral infarction. In addition, there were 3 males and 5 females with similar symptoms in their pedigrees. (2) Histopathological examination of muscle biopsies in this case revealed that there were masses in the sarcolemma, interstitium and myenteric nerve bundles Or particle-like periodic acid Schiff staining positive material deposition, the father muscle biopsy histopathological examination showed no significant abnormalities; (3) GLA enzyme activity in this case slightly decreased, the father was significantly reduced; (4) the case and its The father’s GLA gene test showed a missense mutation of Exon 6 c.837G> C (p.Q279H), a known causative mutation. Conclusion Female patients with Fabry disease may also be the early onset, the incidence of limb ache and limb weakness, fatigue and other symptoms of skeletal muscle involvement may be the main clinical manifestations. Patients with unexplained cardiovascular disease need to rule out the possibility of Fabry disease.