Endocrine Abstracts

Background: Lamin A/C mutations show heterogeneous phenotypes expanding from cardiopathies to lipodystrophies. R482-LMNA gene mutation is the hot-spot for familial partial lipodystrophic syndromes (FPLD2) and is characterized by an increase of intra-abdominal (visceral) fat. In contrast, the visceral fat phenotype of non-R482-LMNA mutated patients has not been well studied.

Objectives: To compare the fat amount and visceral repartition of non-R482, R482-LMNA mutated patients, and non-mutated healthy controls.

Methods: This study included 29 carriers of Non-R482 lamin A/C gene mutation (non-R482 group), 29 R482-LMNA mutated patients, and 19 normal-weight healthy controls, in a single university hospital (Clin.gov2009-AO-1169-48). Body composition (DEXA/MRI), metabolic/inflammatory parameters, and circulating leptin levels were compared between the three groups.

Results: Gender and age did not differ between the two LMNA-mutated groups. R482 carriers had lower BMI (23.9 (22.2; 27.0) vs 27.5 (22.5; 29.4) kg/m²; P<0.05), leptin (5.2 (2.8; 8.0) vs 15.9 (5.2; 22.3) ng/ml; P<0.01), HDL cholesterol (40 (30; 40) vs 48 (40; 50) mg/dl; P<0.05) and fat mass (20 (17.7; 22.8) vs 29.7 (18.7; 38.1) %; P<0.001), and higher intra/total abdominal fat ratio (0.59 (0.47; 0.67) vs 0.36 (0.22; 0.45); P<0.001), fasting blood glucose (117 (94; 199) vs 91 (83; 97) mg/dl; P< 0.001), prevalence of diabetes ((82.7% vs 41.4%); P<0.01) and hypertriglyceridemia (55.2% vs 27.6%; P<0.05) than non-R482 carriers, respectively. In the control group, BMI (22 (21; 24) kg/m²), leptin (4.6 (4.1; 10.7) ng/ml), fasting blood glucose (85 (83; 94) mg/dl, intra/total abdominal fat ratio (0.20 (0.11; 0.30)) were lower, and HDL-cholesterol (56 (44; 70) mg/dl) was higher than in LMNA-mutated patients, whatever the type of mutation. The fat mass (22 (20; 30) %) of the control group was intermediate between the two LMNA-mutated groups.

Conclusion: The non-R482 group had the highest BMI, percentage of fat mass (DEXA), and leptin level of the three groups. The intra/total abdominal fat mass and the frequency of metabolic syndrome were however intermediate between healthy controls (no metabolic syndrome) and FPLD2 who were twice more often diabetic (80%) than non-R482 mutated patients (40%). The visceral fat assessment is one of the most reliable diagnosis criteria of LMNA-mutated syndromes and correlates with the metabolic syndrome.