新生儿葡萄糖/半乳糖吸收不良症2例病例报告并文献复习

目的 探讨以新生儿反复腹泻为主要临床表现的SLC5A1基因致病变异所致葡萄糖/半乳糖吸收不良症的临床特征及其遗传学特点。方法 报告2例新生儿SLC5A1基因复合杂合变异致葡萄糖/半乳糖吸收不良症患儿的临床表现、实验室检查及基因检测结果,并对国内外数据库中有具体临床信息和基因检测结果的相关文献进行复习。结果 2例患儿生后即出现反复腹泻,伴脱水、高钠血症和代谢性酸中毒。全外显子组测序检测到2例患儿均携带SLC5A1基因的复合杂合变异,例1(男)为c.325dupG和c.1107_1109delAGT变异,例2(女)及有相似病史的哥哥均为c.781G>A和c.1298T>C变异。检索PubMed、中国知网、万方和维普数据库,共检索到具有临床资料和基因突变分析的18篇病例报道,与本文合并后共报道74例葡萄糖/半乳糖吸收不良患者。新生儿期最显著的临床表现为腹泻(100%)和脱水(89.2%),换果糖基质奶粉或无碳水化合物配方奶喂养后大便正常。该病患儿通常生后2~5 d即出现腹泻症状,但是亦存在家族内异质性及较晚发病的病例。结论 对于生后不久出现水样便和脱水的患儿,需考虑葡萄糖/半乳糖吸收不良症的可能,并尽早完善基因检测,有助于早期诊断和治疗。

Neonatal glucose/galactose malabsorption: 2 case reports and literature review

Objective To investigate the clinical observations, laboratory tests and genetic characteristics of glucose/galactose malabsorption caused by mutations in SLC5A1 gene.Methods The clinical and genetic features of two glucose/galactose malabsorption children that carried compound heterozygous mutations in SLC5A1 gene were reported, and the related literature from domestic and international databases were reviewed.Results Two patients (one boy and one girl), were referred to the hospital for further evaluation of neonatal onset of watery diarrhea and severe dehydration. The stool was yellow and watery-like and 7-10 times a day. The diarrhea persisted even with lactose-free formula and amino acid-based formula, but ceased when fasted. Whole-exome sequencing revealed compound heterozygous mutations in both patients, indicating a diagnosis of glucose/galactose malabsorption. Patient 1 carried c.325dupG and c.1107_1109delAGT mutations, while patient 2 and her brother with similar symptoms harboured c.781G>A and c.1298T>C mutations. Searching on PubMed, CNKI and Wanfang databases, 18 reports have been discovered to give both the clinical and genetic features, and 74 cases of glucose/galactose malabsorption have been reported, including the two cases in our report. All the patients were recorded with diarrhea of different severity and 89.2% (66/74) with dehydration. The diarrhea has been significantly improved in all patients after the introduction of a fructose-based formula or a carbohydrate-free formula. We examined possible differences in sex, age of onset and the presence of signs and symptoms with mutation type(missence versus other types of mutations). No specific genotype-phenotype correlation could be established.Conclusion For neonates manifested as watery stools and dehydration, glucose/galactose malabsorption should be taken into consideration. Genetic test can help to get an early and accurate diagnosis.