Diagnosis, treatment and genetic analysis of a case of Alstrom syndrome caused by compoud heterozygous mutation of ALMS1.

Alstrom syndrome is a rare autosomal recessive disorder disease caused by mutations in the ALMS1 gene, and its typical clinical manifestations include cone-rod retinal dystrophy, sensorineural deafness, obesity, insulin resistance, diabetes mellitus, hypertriglyceridemia, non-alcoholic fatty liver, dilated cardiomyopathy, and progressive hepatic and renal dysfunction. In this report, we followed up a young male patient presenting with diabetes mellitus, who was later diagnosed with blindness, deafness, hyperlipidemia, obesity, fatty liver, and insulin resistance. Genetic testing revealed a compound heterozygous mutation in ALMS1 from the patient, with an exon 8 c.5535delG (p.S1847Lfs*24) mutation inherited from the maternal side and an exon 16 c.10819C>T (p.R3607X) mutation from the paternal side. Neither of these two mutations had been previously recorded in the known ALMS1 genetic mutation database. Hyperinsulinemic-euglycemic clamp test indicated that the insulin sensitivity index was significantly improved in the patient after taking oral dapagliflozin. By summarizing and analyzing this case, we should consider Alstrom syndrome in clinical adolescent-onset diabetes patients with blindness, deafness, severe insulin resistance, and lipid metabolism disorder. These two new mutation sites identified in this case enrich the genetic mutation database of the ALMS1 gene, and the follow-up data of this study provide new evidence for deciding appropriate glucose-lowering regimens in patients with Alstrom syndrome.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。.