Endocrine metabolism characteristics of Alström syndrome in 25 Chinese patients and identification of a new splice site in the ALMS1 gene.

Background: Alström syndrome is a serious monogenic rare disease with lacking systematic analyses of its endocrine and metabolic characteristics.

Method: Clinical data were obtained from Alström syndrome, and group comparison analyses were conducted. Whole exome sequencing was used for molecular diagnosis, and miniGene experiments were performed for the ALMS1 c.9539G > A mutation.

Result: Twenty-five patients, 14 males and 11 females, with an average age of diagnosis of 7.3 years, were included. Obesity, insulin resistance, diabetes, thyroid nodules and subclinical hypothyroidism, hyperlipidemia, fatty liver, mild scoliosis and sex hormone abnormalities were common endocrine and metabolic abnormalities, whereas hypokalaemia and pancreatitis occurred only in a single case in this cohort. Among patients with Alström syndrome, the 2-h blood glucose and type III procollagen N-terminal peptide (PIIIPN-P) levels in non-obesity group were significantly greater than that in obesity group. And the TG level of Alström syndrome patients in diabetes group was higher than that in non-diabetes group. Nonsense and frameshift mutations were the main types of ALMS1 gene mutations (90%, 45/50), with c.9151_9152delCT and c.10,822 C > T being the two variants with the highest mutation frequency, accounting for 10% and 8%. c.9539G > A is a variant that affects splicing, resulting in 298 bp deletion of exon 10.

Conclusion: Diabetes may exacerbate the development of hyperlipidaemia in Alström syndrome. Obesity management strategies may be adjusted relaxed appropriately for patients with Alström syndrome patients. c.9151_9152delCT and c.10,822 C > T mutations of ALMS1 had the highest variant frequency in this cohort, and c.9539G > A was a new likely pathogenic as splicing variant.