Genetic forms of the cardiometabolic syndrome: what can they tell the clinician?
A well-worn medical aphorism states that "when you hear hoof beats, think of a horse and not a zebra." When applying this principle to the cardiometabolic syndrome (CMS), the horse would be represented by the prevalent CMS phenotype that affects approximately 30% of individuals in Westernized societies, while the zebra is represented by very rare conditions--such as lipodystrophy syndromes--that share some features with the more prevalent CMS. For instance, familial partial lipodystrophy types 2 and 3 result from heterozygous mutations in LMNA, encoding nuclear lamin A/C, and in PPARG, encoding peroxisome proliferator-activated receptor (PPAR)-gamma, respectively. Patients with either subtype of partial lipodystrophy exhibit an increased ratio of central to peripheral fat stores, dysglycemia, dyslipidemia, and hypertension, with predisposition for developing insulin-resistant diabetes and atherosclerosis end points. Sometimes, however, the zebra serves as a model that can help us understand the horse, so that the rare partial lipodystrophies might offer some insight into pathogenesis and treatment of the more prevalent CMS.
Yuan
George
G
Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5K8.
Hegele
Robert A
RA
D006801:Humans; D008060:Lipodystrophy / Q000235:genetics; D052496:Lipodystrophy, Familial Partial / Q000235:genetics / Q000628:therapy; D024821:Metabolic Syndrome / Q000235:genetics*; D009765:Obesity / Q000150:complications