Heterogeneity and causation of organ dysfunction in Alstr?m syndrome

摘要

Alstr?m syndrome (OMIM 203800) is an autosomalrecessive condition caused by pathological mutations inthe ALMS1 gene of worldwide distribution prevalence.200 subjects and longitudinal in depth studies of the UKcohort of 100 subjects have highlighted the extreme variationnot only in the rate of visual and hearing loss butalso in extent and progression of cardiac, renal, hepaticand endocrine dysfunction. The range in age at whichvisual acuity declines to <6/36 and/or when neuronaldeafness is diagnosed is from 5 to 40 years. Life threateningcardiomyopathy occurs in 30% of neonates and canrecur or arise de novo in 25% of all young adults from12 to 25 years of age with sporadic cases later than this.Renal failure (CKD stage 5) occurs from 16 to 50 years in25% of cases and hepatic cirrhosis in 10% between 10and 40 years. Underlying this trend is some degree of cardiacand renal fibrosis and fatty liver in all, and severeinsulin resistance. Progression from insulin resistance totype 2 diabetes and its severity and from fatty liver tofibrosis, then cirrhosis may be halted in early stages bylifestyle improvement especially in the second and thirddecades. Variation in deafness, renal and cardiac fibrosisdiffers within families but shows ethnic clustering suggestivethat modifier genes contribute.