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

ABSTRACT

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.