Type 1 familial partial lipodystrophy: Understanding the Köbberling syndrome

Endocrine. 2016 Nov;54(2):411-421. doi: 10.1007/s12020-016-1002-x.

PMID: 27473102

Cristina Guillín-Amarelle, Sofía Sánchez-Iglesias, Ana Castro-Pais

Highlights: This case-controlled study aimed to characterize this syndrome better by evaluating a group of women with phenotypic features of type 1 familial partial lipodystrophy.

Abstract

Background: Mendelian disorders involving abnormal body fat distribution and insulin resistance are known as familial partial lipodystrophy. The Köbberling syndrome (type 1 familial partial lipodystrophy), which is characterized by fat loss in the lower limbs and abnormal fat accumulation in other areas, is included in the current classification. Although type 1 familial partial lipodystrophy is thought to be heritable, little is known about it, including possible contributing mutations.

Objective and methods: By evaluating a group of women with phenotypic signs of type 1 familial partial lipodystrophy, we were able to better describe this condition. This study compared 98 women with type 1 familial partial lipodystrophy who lacked classical mutations known to cause familial partial lipodystrophy to 60 women without lipodystrophy and 25 patients with type 2 familial partial lipodystrophy in a casecontrolled study (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. For type 1 familial partial lipodystrophy diagnosis, receiver-operating characteristic curve analyses were undertaken, comparing different truncal/limbs ratios.

Results: Patients with type 1 familial partial lipodystrophy exhibited detectable lipodystrophy before adolescence in 68% of cases, and the majority had an autosomal-dominant pattern (86%). Type 1 familial partial lipodystrophy patients had much less lower-limb adipose tissue than women without lipodystrophy, but significantly more than Dunnigan disease patients. Furthermore, metabolic abnormalities were more common in type 1 familial partial lipodystrophy patients (81%) than in non-lipodystrophic patients (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. Type 1 familial partial lipodystrophy had worse metabolic profiles than Dunnigan disease. The best ratio was subscapular/calf skinfolds (KöB index), with a cut-off value of 3.477, according to the receiver-operating characteristic curve analysis (sensitivity: 89%; specificity: 84%).

Conclusion: Type 1 familial partial lipodystrophy was an autosomal-dominant, early-onset lipodystrophy marked by fat loss in the lower limbs and aberrant fat buildup in the abdominal visceral region, which was linked to insulin resistance and metabolic problems. This syndrome is strongly suggested by a KöB index of >3.477.

Keywords: Lipodistrofi, Body composition, Familial partial lipodystrophy, Visceral adipose tissue