Generalized lipodystrophy, congenital and acquired (lipoatrophy)

Abstract

Seip M, Trygstad 0. Generalized lipodystrophy, congenital and acquired (lipoatrophy) Acta Pediatr 1996; Suppl413:2-28. Stockholm. ISSN 0803-5326 This review is based on longitudinal studies on our seven patients with congenital generalized lipodystrophy, our patient with acquired generalized lipodystrophy, and published papers on these subjects. An inability to store energy in adipose tissue is of pathogenetic importance. In congenital lipodystrophy, insulin resistance is present from birth, resulting in hyperinsulinaemia, dyslipidaemia, and insulin-resistant diabetes with an anabolic syndrome worsened by a voracious appetite. Clinically. we observed increased height velocity in pre-school age children, and organomegaly with hypertrophic cardiomyopathy, which seems to be lethal in early adulthood: three of our patients died at the ages of 24,32 and 37 years. The oldest alive, 39 years, suffers from stenocardia. Regarding treatment, it is most important to reduce energy consumption. The congenital form is recessively inherited. The aetiology may be related to insulin receptor or postreceptor mechanisms. Acquired generalized lipodystrophy seems to be an autoimmune disorder with secondary destruction of the adipose organ; the anabolic syndrome with insulin-resistant diabetes is secondary. Our patient died when 24 years old from pneumonia. 0 Acanthosis nigricans. anabolic syndrome, generalized lipodvstrophy, h~vpermetaholism, hypertrophic cardiomyopathy , lipoatrophic diabetes 0 Trygstad, Department of Paediatrics, Rikshospitalet. N-0027 Oslo, Norway cr) Scandinavian University Press 1996. ISSN 0803-5253 Generu1i:ed lipodwtrophy 3 ACTA PEDIATR SUPPL 413 (1W6) Tuhle 1. Main clinical features in generalized lipodystrophy. Congenital type ( Berurdinelli-Seip syndrome) 1. 2. 3. 4. 5. 6. 7. Extreme paucity of fat in subcutaneous and other adipose tissues, with insulin resistance, hyperinsulinaemia, hypertriglyceridaemia, and non-ketotic diabetes Voracious appetite and hypermetabolism, hyperhidrosis An anabolic syndrome with increased height velocity, advanced bone age. muscular hypertrophy, masculine body build, acromegaloid stigmata, organomegaly, enlarged genitalia in infancy, abundant hair of the scalp, hypertrichosis Hypertrophic cardiomyopathy (serious) Acanthosis nigricans Often mild mental retardation Hypothalamic-pituitary dysfunction Acquired type (Seip-Lowrence svndronte)

Leptin Stimulates Ischemia-Induced Retinal Neovascularization

“…It is well recognized that hyperglycemia is one of the possible contributors to the development of diabetic retinopathy (2)(3)(4). In this regard, it is interesting to examine the degree of diabetic retinopathy in patients with lipoatrophic diabetes who have hyperglycemia but hypoleptinemia (27).…”

WAT-free mice: diabetes without obesity

“…In both cases the resulting mice display anatomical and physiological properties very similar to human patients suffering from generalized lipodystrophy. Such patients lack WAT, a condition resulting from either genetic or autoimmune etiologies, and are severely diabetic (Foster 1994;Seip and Trygstad 1996). The present reports provide fresh and interesting observations regarding the physiological consequences of life without fat and, moreover, establish animal models that offer new opportunities for the study of type 2 diabetes.…”

“…Not surprisingly, the answers to this question were fully anticipated by clinical scientists who have studied lipodystrophic patients for the past century (for review, see Seip and Trygstad 1996). Humans suffering from congenital or acquired lipodystrophy become severely diabetic, have voracious appetites, are hypermetabolic, and display an anabolic syndrome that includes organomegaly of the liver, spleen, pancreas, and kidney.…”

“…One simplistic take-home lesson is that type 2 diabetes can result from an imbalance in the abundance of WAT-too little, just as too much, is unhealthy. (Seip and Trygstad 1996).…”

A-ZIP/F-1 mice lacking white fat: a model for understanding lipoatrophic diabetes

“…1,2 Patients with these disorders exhibit a wide range in the distribution of fat loss, from generalized to partial to focal. The age of onset ranges from congenital through adulthood, and is often characteristic of the particular subtype of the disease.…”