title: Type 1 familial partial lipodystrophy: understanding the Köbberling syndrome.
abstract: Familial partial lipodystrophy are Mendelian disorders involving abnormal body fat distribution and insulin resistance. The current classification includes the Köbberling syndrome (type 1 familial partial lipodystrophy), characterized by fat loss in the lower limbs and abnormal fat accumulation in other areas. Type 1 familial partial lipodystrophy appears to be heritable, but little is known about it, including putative contributing mutations. We aimed to characterize this syndrome better by evaluating a group of women with phenotypic features of type 1 familial partial lipodystrophy. This is a case-controlled study in which 98 women with type 1 familial partial lipodystrophy that lacked classical mutations known to cause familial partial lipodystrophy were compared with 60 women without lipodystrophy and 25 patients with type 2 familial partial lipodystrophy (Dunnigan disease). Clinical course, body composition by dual-energy X-ray absorptiometry, HbA1c, lipid profile, insulin, leptin and family history were evaluated in all of the participants. Analyses of receiver-operating characteristic curve were performed for type 1 familial partial lipodystrophy diagnosis, comparing different truncal/limbs ratios. Among patients with type 1 familial partial lipodystrophy, 68 % developed recognizable lipodystrophy before adolescence, and most displayed an autosomal-dominant pattern (86 %). Women with type 1 familial partial lipodystrophy had less lower-limb adipose tissue than women without lipodystrophy, but significantly more than patients with Dunnigan disease. Moreover, metabolic disturbances occurred more frequently in the type 1 familial partial lipodystrophy group (81 %) than in the non-lipodystrophic group (30 %, p<0.05). The severity of metabolic disturbances was inversely proportional to the percentage of fat in the lower extremities and directly proportional to the amount of visceral adipose tissue. Metabolic profiles were worse in type 1 familial partial lipodystrophy than in Dunnigan disease. According to the receiver-operating characteristic curve analysis, the best ratio was subscapular/calf skinfolds (KöB index), with a cut-off value of 3.477 (sensitivity: 89 %; specificity: 84 %). Type 1 familial partial lipodystrophy was an early-onset, autosomal-dominant lipodystrophy, characterized by fat loss in the lower limbs and abnormal fat accumulation in the abdominal visceral region, associated to insulin resistance and metabolic disorders. A KöB index >3.477 is highly suggestive of this syndrome.
authors.affiliation: UETeM-Molecular Pathology Group, Department of Medicine, IDIS-CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Guillín-Amarelle
authors.affiliation: UETeM-Molecular Pathology Group, Department of Medicine, IDIS-CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Sánchez-Iglesias
authors.affiliation: Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Castro-Pais
authors.affiliation: UETeM-Molecular Pathology Group, Department of Medicine, IDIS-CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Rodriguez-Cañete
authors.affiliation: Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Ordóñez-Mayán
authors.affiliation: Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Pazos
authors.affiliation: UETeM-Molecular Pathology Group, Department of Medicine, IDIS-CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: González-Méndez
authors.affiliation: UETeM-Molecular Pathology Group, Department of Medicine, IDIS-CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rodríguez-García
authors.affiliation: Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.affiliation: Department of Paediatrics, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Marmiesse
authors.affiliation: UETeM-Molecular Pathology Group, Department of Medicine, IDIS-CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain. david.araujo@usc.es.|Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain. david.araujo@usc.es.
authors.forename: David
authors.initials: D
authors.lastname: Araújo-Vilar
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D001823:Body Composition / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood*; D052496:Lipodystrophy, Familial Partial / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging; D008875:Middle Aged; D010641:Phenotype; D063189:Symptom Assessment
chemical_list: D007328:Insulin; D020738:Leptin; D008055:Lipids
keywords: Body composition; Familial partial lipodystrophy; Visceral adipose tissue