目的:先天性蔗糖酶-异麦芽糖酶缺乏症是一种以慢性渗透性腹泻为特征的常染色体隐性遗传二糖酶缺乏症。在这项研究中,研究了一例先天性蔗糖酶-异麦芽糖酶缺乏症患者近亲属的基因型-表型关系.
方法:一名23个月大的女性患者,具有蔗糖酶-异麦芽糖酶基因c.317G>A(p。C106Y)纯合突变被诊断为索引病例,随后进行了她的谱系分析。在临床症状方面比较了有和没有蔗糖酶-异麦芽糖酶基因突变的家族成员。
结果:该研究包括109例[平均年龄±SD:22.6±17.2岁(0.1-75岁),指数病例130名家庭成员中的61名男性(56%)]。蔗糖酶-异麦芽糖酶基因c.317G>A(p。C106Y)杂合突变27例(24.7%),男性14例(51.9%),平均年龄23.2±18.3岁。12例(44.4%)有症状的突变患者中最常见的主诉是腹痛(37%)。气体烦躁(33.3%),腹胀(22.2%),及臭臭粪便(百分之十八点五)。与无突变的病例相比,在气体烦躁的发生率方面观察到了统计学上的显着差异,臭臭的凳子,≥2个胃肠道症状,餐后投诉,和食物过敏(分别为P=.005,P=.047,P=.049,P=.017,P=.021)。对7例症状随饮食消除而未改善的患者应用了糖糖苷酶替代。酶处理后获得临床响应。
结论:尽管其常染色体隐性遗传,先天性蔗糖酶-异麦芽糖酶缺乏症在杂合子个体中也有症状.需要进一步的研究来阐明基因型-表型关系和疾病的管理。
OBJECTIVE: Congenital sucrase-isomaltase deficiency is an autosomal recessive inherited disaccharidase deficiency characterized by chronic osmotic diarrhea. In this study, the genotype-phenotype relationships of close relatives of an index case with congenital sucrase-isomaltase deficiency were investigated.
METHODS: A 23-month-old female patient with a sucrase-isomaltase gene c.317G>A (p.C106Y) homozygous mutation was diagnosed as an index case and her
pedigree analysis was performed subsequently. The family members with and without sucrase- isomaltase gene mutations were compared in terms of clinical symptoms.
RESULTS: The study included 109 cases [mean age ± SD: 22.6 ± 17.2 years (0.1-75 years), 61 males (56%)] of 130 family members of the index case. Sucrase-isomaltase gene c.317G>A (p.C106Y) heterozygous mutation was detected in 27 cases (24.7%); 14 (51.9%) were male and had a mean age of 23.2 ± 18.3 years. The most common complaints of 12 (44.4%) symptomatic patients with mutations were abdominal pain (37%), gas irritability (33.3%), bloating (22.2%), and foul-smelling stools (18.5%). Compared with the cases without mutation, a statistically significant difference was observed in the incidence of gas irritability, foul-smelling stool, ≥2 gastrointestinal symptoms, postprandial complaints, and food allergy (P = .005, P = .047, P = .049, P = .017, P = .021, respectively). Sacrosidase enzyme replacement was applied to 7 patients whose symptoms did not improve with dietary elimination. Clinical response was obtained after enzyme treatment.
CONCLUSIONS: Despite its autosomal recessive inheritance, congenital sucrase-isomaltase deficiency can also be symptomatic in heterozygous individuals. Further studies are required to clarify the genotype-phenotype relationship and management of the disease.