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Nat Rev Endocrinol. 2015 Sep;11(9):522-34. doi: 10.1038/nrendo.2015.123. Epub 2015 Aug 4.

Congenital generalized lipodystrophies--new insights into metabolic dysfunction.

Author information

1
Division of Paediatric Endocrinology, Department of Paediatrics, Department of Internal Medicine, Centre for Human Nutrition, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8537, USA.
2
Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8537, USA.

Abstract

Congenital generalized lipodystrophy (CGL) is a heterogeneous autosomal recessive disorder characterized by a near complete lack of adipose tissue from birth and, later in life, the development of metabolic complications, such as diabetes mellitus, hypertriglyceridaemia and hepatic steatosis. Four distinct subtypes of CGL exist: type 1 is associated with AGPAT2 mutations; type 2 is associated with BSCL2 mutations; type 3 is associated with CAV1 mutations; and type 4 is associated with PTRF mutations. The products of these genes have crucial roles in phospholipid and triglyceride synthesis, as well as in the formation of lipid droplets and caveolae within adipocytes. The predominant cause of metabolic complications in CGL is excess triglyceride accumulation in the liver and skeletal muscle owing to the inability to store triglycerides in adipose tissue. Profound hypoleptinaemia further exacerbates metabolic derangements by inducing a voracious appetite. Patients require psychological support, a low-fat diet, increased physical activity and cosmetic surgery. Aside from conventional therapy for hyperlipidaemia and diabetes mellitus, metreleptin replacement therapy can dramatically improve metabolic complications in patients with CGL. In this Review, we discuss the molecular genetic basis of CGL, the pathogenesis of the disease's metabolic complications and therapeutic options for patients with CGL.

PMID:
26239609
DOI:
10.1038/nrendo.2015.123
[Indexed for MEDLINE]

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