Novel Forms of Lipodystrophy

Lipodystrophies are a heterogeneous group of conditions in which individuals never develop or progressively lose adipose tissue in parts or all of their bodies (1,2) (Table 1). In this commentary, we will make the case that 1 ) defining lipodystrophy is a work in progress; 2 ) not all forms of lipodystrophy are very rare; 3 ) lipodystrophy and obesity can occur simultaneously and their metabolic consequences are similar and possibly synergistic; 4 ) leptin treatment can have impressive therapeutic effects; and 5 ) these conditions provide useful paradigms to explore the role of the adipose tissue on metabolic homeostasis and to investigate pathways leading from distinct genetic mutations to very different clinical phenotypes. View this table: Table 1 Phenotypic characterization of lipodystrophy subtypes with inclusion of genotype (if available) What is lipodystrophy? A recent consensus statement by the American Association of Clinical Endocrinologists acknowledges the difficulty in determining quantitative criteria and concludes that “lipodystrophy is a condition characterized by regional or total loss or absence of subcutaneous fat. This can occur either in the presence or absence of metabolic abnormalities, and with diverse clinical presentations. While generalized forms of lipodystrophy are often diagnosed during childhood or adolescence, some forms of lipodystrophy, particularly familial partial lipodystrophy, may bear some resemblance to common metabolic disorders managed by adult endocrinologists” (3). There are no specific cutoff levels for percent body fat or leptin concentrations, and it often requires time and long-term follow-up to confirm the diagnosis. Much progress has been made in identifying the genetic etiologies of many lipodystrophy forms (1). How missing or abnormal gene products prevent adipocyte development or cause disappearance of adipose tissue in distinct regions of the human body, however, remains mostly unknown. An excellent example is familial partial lipodystrophy or Dunnigan syndrome, in which numerous mutations of the LMNA gene have been found. LMNA is …