中华实用儿科临床杂志
中華實用兒科臨床雜誌
중화실용인과림상잡지
Journal of Applied Clinical Pediatrics
2015年
20期
1521-1524
,共4页
新生儿糖尿病%遗传学%磺脲类药物
新生兒糖尿病%遺傳學%磺脲類藥物
신생인당뇨병%유전학%광뇨류약물
Neonatal diabetes mellitus%Genetics%Sulfonylureas
新生儿糖尿病（neonatal diabetes mellitus，NDM）是出生6个月内出现的一种罕见的单基因糖尿病。根据转归分为暂时性新生儿糖尿病（ transient neonatal diabetes mellitus，TNDM）和永久性新生儿糖尿病（permanent neonatal diabetes mellitus，PNDM），二者约各占50％。TNDM 婴儿期缓解，青春期或成年早期复发， PNDM 无缓解期。两者在临床表现上有重叠，需要长期随访进行分型。PNDM 的致病基因有20余种，其中最常见的是编码 ATP 敏感钾通道（KATP ）Kir6.2和 SUR1亚单位的 KCNJII 和 ABCC8，其次为 INS。TNDM 的70％由6q24印迹区域父源基因的过度表达引起，26％由 KCNJII、ABCC8、INS 和 HNFIB 突变所致。磺脲类药物通过关闭 KATP促进胰岛素的释放可以治疗 KATP突变引起的高血糖，并且改善患儿的神经系统症状，但仍有10％的KCNJII和15％ ABCC8突变者不能实现胰岛素到格列苯脲的转换。分子诊断有助于 NDM 的分型、判断预后及实现个体化治疗。
新生兒糖尿病（neonatal diabetes mellitus，NDM）是齣生6箇月內齣現的一種罕見的單基因糖尿病。根據轉歸分為暫時性新生兒糖尿病（ transient neonatal diabetes mellitus，TNDM）和永久性新生兒糖尿病（permanent neonatal diabetes mellitus，PNDM），二者約各佔50％。TNDM 嬰兒期緩解，青春期或成年早期複髮， PNDM 無緩解期。兩者在臨床錶現上有重疊，需要長期隨訪進行分型。PNDM 的緻病基因有20餘種，其中最常見的是編碼 ATP 敏感鉀通道（KATP ）Kir6.2和 SUR1亞單位的 KCNJII 和 ABCC8，其次為 INS。TNDM 的70％由6q24印跡區域父源基因的過度錶達引起，26％由 KCNJII、ABCC8、INS 和 HNFIB 突變所緻。磺脲類藥物通過關閉 KATP促進胰島素的釋放可以治療 KATP突變引起的高血糖，併且改善患兒的神經繫統癥狀，但仍有10％的KCNJII和15％ ABCC8突變者不能實現胰島素到格列苯脲的轉換。分子診斷有助于 NDM 的分型、判斷預後及實現箇體化治療。
신생인당뇨병（neonatal diabetes mellitus，NDM）시출생6개월내출현적일충한견적단기인당뇨병。근거전귀분위잠시성신생인당뇨병（ transient neonatal diabetes mellitus，TNDM）화영구성신생인당뇨병（permanent neonatal diabetes mellitus，PNDM），이자약각점50％。TNDM 영인기완해，청춘기혹성년조기복발， PNDM 무완해기。량자재림상표현상유중첩，수요장기수방진행분형。PNDM 적치병기인유20여충，기중최상견적시편마 ATP 민감갑통도（KATP ）Kir6.2화 SUR1아단위적 KCNJII 화 ABCC8，기차위 INS。TNDM 적70％유6q24인적구역부원기인적과도표체인기，26％유 KCNJII、ABCC8、INS 화 HNFIB 돌변소치。광뇨류약물통과관폐 KATP촉진이도소적석방가이치료 KATP돌변인기적고혈당，병차개선환인적신경계통증상，단잉유10％적KCNJII화15％ ABCC8돌변자불능실현이도소도격렬분뇨적전환。분자진단유조우 NDM 적분형、판단예후급실현개체화치료。
Neonatal diabetes mellitus(NDM)occurs within the first 6 months of life. Depending on clinical outcomes,it is classified into transient neonatal diabetes mellitus(TNDM)and permanent neonatal diabetes mellitus (PNDM). TNDM,which accounts for 50% of NDM goes into remission after treatment for an average period of 12 weeks,but relapse in puberty and early adulthood. PNDM,on the other hand,is a lifelong disease without remission. The clinical features of TNDM and PNDM overlap,and the typing is based on clinical remission on follow - up. More than 20 pathogenic genes have been identified in PNDM,of which the most common are KCNJII and ABCC8 encoding the Kir6. 2 and SUR1 subunits of KATP channel accounting for 50% . TNDM is caused by defects associated with overexpres-sion of paternally expressed genes in the imprinted region of chromosome 6q24 in 70% cases. About 26% of the defects contain mutations in KCNJII,ABCC8,INS or HNFIB. In vitro and clinical studies suggest that treatment with oral sul-fonylurea can close KATP channel and improve glycemic control and neuropsychological development. However,10% of patients with KCNJII and 15% ABCC8 mutations fail to achieve glycemic control when insulin therapy is switched to o-ral sulfonylureas. Therefore,molecular diagnosis is vital not only in accurate typing but also for better prognostication.
