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Lipodystrophies

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Abstract

The lipodystrophies are rare disorders characterized by selective but variable loss of adipose tissue. Metabolic complications, such as insulin resistance, diabetes mellitus, hypertriglyceridemia, and fatty liver, increase in severity with the extent of fat loss. The lipodystrophies can be classified into two major types: familial and acquired. The main subtypes of familial lipodystrophies are congenital generalized lipodystrophy, an autosomal recessive disorder characterized by near complete lack of metabolically active adipose tissue from birth, and familial partial lipodystrophy, Dunnigan type, an autosomal dominant disorder characterized by loss of subcutaneous fat from the extremities at puberty and excess fat accumulation in the face and neck. Recently, a gene for congenital generalized lipodystrophy was localized to chromosome 9q34, and a gene for familial partial lipodystrophy, Dunnigan type, to chromosome 1q21–22; the genes, however, remain to be identified. Patients with acquired generalized lipodystrophy have generalized loss of subcutaneous fat, but those with acquired partial lipodystrophy have fat loss limited to the face, trunk, and upper extremities. Both varieties occur approximately three times more often in women, begin during childhood, and have underlying autoimmunity. Patients infected with the human immunodeficiency virus (HIV) who are receiving therapy that includes HIV-1 protease inhibitors have been reported to develop a lipodystrophy characterized by loss of subcutaneous fat from the extremities and face but excess fat deposition in the neck and trunk. Localized lipodystrophies can be caused by drugs, pressure, panniculitis, or unknown mechanisms. Current management of patients includes cosmetic surgery, diet, and drug therapy for control of diabetes and dyslipidemia.

Section snippets

Congenital generalized lipodystrophy (Berardinelli-Seip syndrome)

Congenital generalized lipodystrophy [Online Mendelian Inheritance in Man (OMIM) 269700] is an extremely rare autosomal recessive disorder reported initially by Berardinelli (3) and Seip (4). It affects all ethnic groups. Assuming that the published reports of approximately 120 affected subjects during 44 years reflect roughly 25% ascertainment, its prevalence is estimated to be less than 1 case in 12 million people.

Acquired generalized lipodystrophy (Lawrence syndrome)

Acquired generalized lipodystrophy was initially reported by Ziegler (43); subsequently, Lawrence (44) provided a detailed clinical description and autopsy findings in a 26-year-old woman. Lawrence proposed five major diagnostic criteria: generalized absence of fat, insulin resistant diabetes mellitus, absence of ketosis, elevated basal metabolic rate, and severe hyperlipidemia with hepatomegaly (44). These criteria, however, fail to distinguish the acquired variety from the congenital variety

Differential diagnosis of lipodystrophies

Patients with lipodystrophies should be differentiated from patients with SHORT syndrome [short stature, hyperextensibility of joints, ocular depression, Reiger (ocular and dental) anomaly, and teething delay; OMIM 269880], some of whom lose subcutaneous fat from the face, upper extremities, chest, and abdomen; patients with Werner syndrome (OMIM 277700), who have thin limbs but whose subcutaneous fat is well preserved; patients with neonatal progeroid syndrome (Wiedemann-Rautenstrauch

Cosmetic management

Cosmetic management of patients with lipodystrophy involves facial reconstruction with free flaps, transposition of facial muscle, and silicone or other implants in the cheeks. In some patients with acquired partial lipodystrophy, adipose tissue transplantation from the abdomen or hip to the face is not successful, but in others it lasts for several years (personal experience, 96, 97, 98). Several of my patients with familial partial lipodystrophies have undergone liposuction or lipectomy for

Acknowledgements

The author is indebted to Dr. Daniel W. Foster for introducing me to the syndromes of lipodystrophies; to Dr. Foster and Dr. David Hillis for critical review of the manuscript; to Dr. Scott M. Grundy for his continued support and encouragement; Dr. Anne Bowcock for genetic studies; Drs. James Fleckenstein and Ronald M. Peshock for MRI studies; Dr. Franklin Vuitch for histopathology studies; Drs. Manisha Chandalia and Dali Chen for clinical evaluation of patients; Drs. James Stray-Gundersen and

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    Supported in part by National Institutes of Health Grants R01-DK54387, M01-RR00633 and the Southwestern Medical Foundation.

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