CAJ | 학술논문

目的分析1例先天性失氯性腹泻患儿的临床和SLC26A3基因突变特点,以提高对本病的认识.方法收集2014年6月于首都儿科研究所附属儿童医院诊治的先天性失氯性腹泻患儿的临床资料,抽取患儿及其父母静脉血2 mL,利用DNA提取试剂盒获取基因组DNA,应用PCR和DNA直接测序方法进行SLC26A3基因突变检测.结果患儿临床表现为母孕期羊水过多、早产,出生体质量正常.出生后早期出现水样便、体质量不增.电解质提示顽固性低氯血症、低钾血症、低钠血症.血气分析示顽固性代谢性碱中毒,血管升压素及醛固酮升高.尿氯减少,而大便Cl-明显增多(＞90 mmol/L).予口服氯化钾[3 mmol/(kg·d)]及氯化钠[4 mmol/(kg·d)]替代治疗后电解质紊乱好转,碱中毒减轻,生长发育得到改善.基因分析显示患者SLC26A3基因第15外显子1631位点T＞A纯合突变,导致异亮氨酸544天冬酰胺突变,改变了SLC26A3的跨膜蛋白序列,导致Cl-/HCO3-交换障碍.患儿父母相同位点杂合突变,其父母临床表型正常.结论先天性失氯性腹泻是临床罕见的常染色体隐性遗传性疾病,易误诊.出生早期出现腹泻伴持续性低氯、低钠、低钾血症和代谢性碱中毒者要考虑本病可能,基因分析可协助诊断.早期诊断及氯化钾/氯化钠替代治疗对患者的预后十分关键.
목적 분석1례선천성실록성복사환인적림상화SLC26A3기인돌변특점,이제고대본병적인식.방법 수집2014년6월우수도인과연구소부속인동의원진치적선천성실록성복사환인적림상자료,추취환인급기부모정맥혈2 mL,이용DNA제취시제합획취기인조DNA,응용PCR화DNA직접측서방법진행SLC26A3기인돌변검측.결과 환인림상표현위모잉기양수과다、조산,출생체질량정상.출생후조기출현수양편、체질량불증.전해질제시완고성저록혈증、저갑혈증、저납혈증.혈기분석시완고성대사성감중독,혈관승압소급철고동승고.뇨록감소,이대편Cl-명현증다(＞90 mmol/L).여구복록화갑[3 mmol/(kg·d)]급록화납[4 mmol/(kg·d)]체대치료후전해질문란호전,감중독감경,생장발육득도개선.기인분석현시환자SLC26A3기인제15외현자1631위점T＞A순합돌변,도치이량안산544천동선알돌변,개변료SLC26A3적과막단백서렬,도치Cl-/HCO3-교환장애.환인부모상동위점잡합돌변,기부모림상표형정상.결론 선천성실록성복사시림상한견적상염색체은성유전성질병,역오진.출생조기출현복사반지속성저록、저납、저갑혈증화대사성감중독자요고필본병가능,기인분석가협조진단.조기진단급록화갑/록화납체대치료대환자적예후십분관건.
Objective To analyze the clinical characteristics and mutation of SLC26A3 gene of a patient with congenital chloride diarrhea in order to deepen the understanding of the disease.Methods The clinical data of the patient who was admitted in Affiliated Hospital of Capital Pediatric Institute in June 2014 were collected.Venous blood of the proband and his parents (2 mL for each) had been extracted for genomic DNA isolation.The 21 exons of SLC26A3 gene were amplified with polymerase chain reaction and screened for mutations by sequencing.Results The main clinical features of the patient included polyhydramnios,preterm,normal birth weight,watery diarrhea,low weight and severe electrolyte disturbances with hypochloremia,hypokalemia,hyponatremia and metabolic alkalosis.Renin angiotensin and aldosterone were high.His urine chloride concentration was low and fecal chloride concentration was high (＞ 90mmol/L).After oral salt substitution therapy with KCl and NaCl [3 mmol/(kg · d),4 mmol/(kg · d)],the electrolyte was better,alkalosis was alleviated,and growth and development were improved.The gene analysis revealed that the patient carried nt1631T ＞ A homozygous mutation on exon 15 which lead to Ile544Asn mutation in the predicted SLC26A3 transmembrane protein sequence,which was considered to be responsible for the functional abnormality of the Cl-/HCO3-protein.His parents were carriers of SLC26A3 gene and their clinical phenotype was normal.Conclusions Congenital chloride diarrhea is a rare autosomal recessive disorder and easily misdiagnosed.The patient of early postnatal diarrhea with persistent hypochloremia,hypokalemia,hyponatremia and metabolic alkalosis should be thought about this disease.Genetic analysis can help make the diagnosis.The prognosis is good if a patient has an early diagnosis and appropriate management.