中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2014年
4期
428-432
,共5页
肉碱缺乏%多种酰基辅酶A缺乏%ETFDH基因%SLC22A5基因
肉堿缺乏%多種酰基輔酶A缺乏%ETFDH基因%SLC22A5基因
육감결핍%다충선기보매A결핍%ETFDH기인%SLC22A5기인
Carnitine deficiency%Multiple acyl-CoA dehydrogenase deficiency%ETFDH gene%SLC22A5 gene
目的 对1例误诊为原发性肉碱缺乏症(primary carnitine deficiency,PCD)的核黄素反应型多种酰基辅酶A脱氢酶缺乏症(riboflavin responsive-multiple acyl-CoA dehydrogenase deficiency,RR-MADD)患儿及父母进行基因突变分析,以确定息儿的致病基因突变及误诊的原因.方法 分析1例误诊为原发性肉碱缺乏症并用肉碱治疗7年的RR-MADD患儿的临床表型和腓肠肌活检的电镜检查特点,对患儿及父母进行电子转运黄素蛋白脱氢酶(electron transfer flavoprotein dehydrogenase,ETFDH)基因及肉碱转运蛋白基因(SLC22A5)进行突变检测.结果 患儿肌肉活检的电镜观察显示大量脂质沉积.基因测序结果显示患儿的ETFDH基因第3外显子存在c.250G＞A和c.380T＞C复合杂合突变,患儿的父母分别为c.380T＞C和c.250G＞A的杂合突变携带者.患儿SLC22A5的基因测序未发现致病突变.患儿经基因确诊后同时补充肉碱与大剂量核黄素,病情得到改善.结论 ETFDH基因第3外显子c.250G＞A突变(p.Ala84Thr)是我国南方人群中的1个突变热点,而c.380T＞C突变(p.Leu127Pro)在我国人群中罕有报道.该误诊提示诊断性治疗效果不能替代基因检测.单纯补充肉碱治疗RR-MADD可控制病情达7年,其原因有待于进一步探讨.
目的 對1例誤診為原髮性肉堿缺乏癥(primary carnitine deficiency,PCD)的覈黃素反應型多種酰基輔酶A脫氫酶缺乏癥(riboflavin responsive-multiple acyl-CoA dehydrogenase deficiency,RR-MADD)患兒及父母進行基因突變分析,以確定息兒的緻病基因突變及誤診的原因.方法 分析1例誤診為原髮性肉堿缺乏癥併用肉堿治療7年的RR-MADD患兒的臨床錶型和腓腸肌活檢的電鏡檢查特點,對患兒及父母進行電子轉運黃素蛋白脫氫酶(electron transfer flavoprotein dehydrogenase,ETFDH)基因及肉堿轉運蛋白基因(SLC22A5)進行突變檢測.結果 患兒肌肉活檢的電鏡觀察顯示大量脂質沉積.基因測序結果顯示患兒的ETFDH基因第3外顯子存在c.250G＞A和c.380T＞C複閤雜閤突變,患兒的父母分彆為c.380T＞C和c.250G＞A的雜閤突變攜帶者.患兒SLC22A5的基因測序未髮現緻病突變.患兒經基因確診後同時補充肉堿與大劑量覈黃素,病情得到改善.結論 ETFDH基因第3外顯子c.250G＞A突變(p.Ala84Thr)是我國南方人群中的1箇突變熱點,而c.380T＞C突變(p.Leu127Pro)在我國人群中罕有報道.該誤診提示診斷性治療效果不能替代基因檢測.單純補充肉堿治療RR-MADD可控製病情達7年,其原因有待于進一步探討.
목적 대1례오진위원발성육감결핍증(primary carnitine deficiency,PCD)적핵황소반응형다충선기보매A탈경매결핍증(riboflavin responsive-multiple acyl-CoA dehydrogenase deficiency,RR-MADD)환인급부모진행기인돌변분석,이학정식인적치병기인돌변급오진적원인.방법 분석1례오진위원발성육감결핍증병용육감치료7년적RR-MADD환인적림상표형화비장기활검적전경검사특점,대환인급부모진행전자전운황소단백탈경매(electron transfer flavoprotein dehydrogenase,ETFDH)기인급육감전운단백기인(SLC22A5)진행돌변검측.결과 환인기육활검적전경관찰현시대량지질침적.기인측서결과현시환인적ETFDH기인제3외현자존재c.250G＞A화c.380T＞C복합잡합돌변,환인적부모분별위c.380T＞C화c.250G＞A적잡합돌변휴대자.환인SLC22A5적기인측서미발현치병돌변.환인경기인학진후동시보충육감여대제량핵황소,병정득도개선.결론 ETFDH기인제3외현자c.250G＞A돌변(p.Ala84Thr)시아국남방인군중적1개돌변열점,이c.380T＞C돌변(p.Leu127Pro)재아국인군중한유보도.해오진제시진단성치료효과불능체대기인검측.단순보충육감치료RR-MADD가공제병정체7년,기원인유대우진일보탐토.
Objective To identify pathogenic mutation in a boy affected with riboflavin responsive-multiple acyl-CoA dehydrogenase deficiency (RR-MADD).Methods The patient was initially diagnosed as primary carnitine deficiency (PCD) and has been treated with carnitine supplementation for 7 years.Clinical manifestations and characteristics of fibula muscle specimen were analyzed.Potential mutation in electron transfer flavoprotein dehydrogenase (ETFDH) gene (for the patient and his parents) and carnitine transfer protein gene (SLC22A5) (for the patient) was screened.Results Electronic microscopy of the muscle specimen has suggested lipid storage myopathy.Mutation analysis has found that the patient carried compound heterozygous mutations,c.250G＞A and c.380T＞C,in exon 3 of the ETFDH gene,whilst his father and mother were heterozygous for the c.380T＞C and c.250G＞A mutations,respectively.Screening of the SLC22A5 gene has yielded no clinically meaningful result.After the establishment of diagnosis of RR-MADD,the condition of the patient has improved greatly with supplementation of high doses of riboflavin along with continuous carnitine supplement.Conclusion The c.250G＞A (p.Ala84Thr) mutation of exon 3 of the ETFDH gene has been a hot spot in Southern Chinese population,whilst the c.380T＞C (p.Leu127Pro) is rarely reported.Our case has suggested that therapeutic diagnosis cannot substitute genetic testing.The mechanism for having stabilized the patient with only carnitine supplementation for 7 years needs further investigation.
