遗传 ›› 2022, Vol. 44 ›› Issue (12): 1148-1157.doi: 10.16288/j.yczz.22-217
杨慧杰(), 李德(), 白卉泠, 张铭, 黄俊, 袁小青()
收稿日期:
2022-08-12
修回日期:
2022-09-30
出版日期:
2022-12-20
发布日期:
2022-10-14
通讯作者:
袁小青
E-mail:huijiexiaojie@126.com;lide93207@sina.com;adiposeyy@126.com
作者简介:
杨慧杰,硕士,主治医师,研究方向:内分泌代谢疾病。E-mail:基金资助:
Huijie Yang(), De Li(), Huiling Bai, Ming Zhang, Jun Huang, Xiaoqing Yuan()
Received:
2022-08-12
Revised:
2022-09-30
Online:
2022-12-20
Published:
2022-10-14
Contact:
Yuan Xiaoqing
E-mail:huijiexiaojie@126.com;lide93207@sina.com;adiposeyy@126.com
Supported by:
摘要:
Alstrom综合征是一种由ALMS1基因突变导致的罕见的常染色体隐性遗传病,以锥杆型视网膜营养不良、感音神经性耳聋、肥胖、胰岛素抵抗、糖尿病、高甘油三酯血症、非酒精性脂肪肝、扩张性心肌病、进行性肝肾功能障碍为典型临床表现。本文随访1例以糖尿病就诊的青年男性患者,合并有失明、耳聋、高脂血症、肥胖、脂肪肝、胰岛素抵抗,基因检测结果表明患者ALMS1基因发生复合杂合突变,分别来源于母亲和父亲,前者为8号外显子携带的突变c.5535delG (p.S1847Lfs*24),后者为16号外显子携带的突变 c.10819C>T (p.R3607X),这两个突变位点在已知的ALMS1基因变异库中均未被报道。该患者口服达格列净后,高胰岛素正葡萄糖钳夹实验发现其胰岛素敏感性指数显著提高。通过总结分析该病例,对于临床上青少年起病的合并有失明、耳聋、严重胰岛素抵抗和脂代谢紊乱的糖尿病患者,应考虑到Alstrom综合征的可能。本病例发现的2个新突变位点丰富了ALMS1基因的遗传变异数据库,其治疗随访数据为该类疾病患者选择合适的降糖方案提供了新的证据。
杨慧杰, 李德, 白卉泠, 张铭, 黄俊, 袁小青. 一例ALMS1基因复合杂合突变所致的Alstrom综合征的诊疗和基因检测分析[J]. 遗传, 2022, 44(12): 1148-1157.
Huijie Yang, De Li, Huiling Bai, Ming Zhang, Jun Huang, Xiaoqing Yuan. Diagnosis, treatment and genetic analysis of a case of Alstrom syndrome caused by compoud heterozygous mutation of ALMS1[J]. Hereditas(Beijing), 2022, 44(12): 1148-1157.
表2
患者治疗随访的临床数据"
日期 | 2018年2月 | 2018年11月 | 2019年1月 | 2020年1月 | 2020年9月 | 2021年2月 | 2022年5月 |
---|---|---|---|---|---|---|---|
年龄(岁) | 21 | 22 | 22 | 23 | 24 | 24 | 25 |
体重(kg) | 80 | 80 | - | - | - | 76 | 74.2 |
体重指数(kg/m2) | 30.1 | 30.1 | - | - | - | 28.6 | 27.9 |
血压(mmHg) | 115/78 | 132/74 | - | - | - | 131/65 | 115/78 |
血红蛋白(130~175 g/L) | 170 | 176 | - | - | - | 176 | 189 |
谷丙转氨酶(9~50 U/L) | 64 | 81.6 | 64 | - | 77 | 36 | 55.6 |
谷草转氨酶 (15~40 U/L) | 52 | 90.7 | 39 | 99 | 61 | 31.9 | 51.1 |
r-谷氨酰转肽酶 (10~60 U/L) | 240 | 449 | 143 | - | 202 | 131 | 290 |
空腹血糖 (3.9~6.1 mmol/L) | 12.93 | 10.15 | 8.27 | 15.7 | 15.41 | 4.94 | 12.91 |
尿素氮 (3.1~8.0 mmol/L) | 7.3 | 7.8 | 7.3 | 8 | 7.2 | 9.5 | 10.7 |
肌酐(45~105 μmol/L) | 101.2 | 140 | 144 | 129.9 | 139 | 155 | 182 |
肾小球滤过率 (80~120 ml/min1.73m2) | 85.77 | 58.42 | - | - | - | 51.04 | 42.05 |
尿微白蛋白/肌酐 (<30 mg/g) | 270 | 462.2 | 400.5 | - | - | 414.4 | >300 |
尿酸(90~420 μmol/L) | 524.8 | 653 | 687 | - | 835 | 315 | 439 |
甘油三酯 (0.11~2.26 mmol/L) | 8.87 | 19.51 | 2.96 | - | 12.76 | 3.25 | 8.58 |
总胆固醇 (2~5.2 mmol/L) | 6.41 | 8.18 | 5.85 | - | 7.34 | 5.15 | 8.41 |
低密度胆固醇 (0~3.12 mmol/L) | 5 | 4.5 | 3.88 | - | 2.67 | 3.25 | 5.02 |
糖化血红蛋白(4%~6%) | 11.4 | 13.1 | - | - | 11.1 | 11.3 | 12.3 |
C-肽0 min (370~1470 pmol/L) | 2617 | 2584 | - | - | 2859 | 3890 | 2903 |
C-肽60 min | 4083 | 3993 | - | - | - | 5242 | 3000 |
C-肽120 min | 4992 | 3923 | - | - | - | 5728 | 4013 |
胰岛素敏感指数 (钳夹实验) | - | 0.216 | - | - | - | 1.045 | - |
内脏脂肪(<100 cm2) | 96 | 86 | - | - | - | 84 | 80 |
皮下脂肪(cm2) | 138 | 172 | - | - | - | 142 | 139 |
肝脏脂肪含量(<5%) | - | 14%~17% | - | - | - | 14%~17% | 16% |
肝脏硬度(<9.7 kPa) | - | - | - | - | - | 8.6 | 7.3 |
脂肪衰减(<240 dM/m) | - | - | - | - | - | 309 | 313 |
降糖方案 | 地特36 IU天; 赖脯42 IU/天; 二甲双胍; 吡格列酮; | 二甲双胍; 吡格列酮; 达格列净; | 二甲双胍; 吡格列酮; 达格列净; | 二甲双胍; 吡格列酮; 达格列净; | 二甲双胍; 吡格列酮; 达格列净; | 地特20 IU/天; 二甲双胍; 吡格列酮; 达格列净; 度拉糖肽; | 地特20 IU/天; 吡格列酮; 达格列净; 度拉糖肽; |
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