Endocrine Abstracts

Familial Partial Lipodystrophy Syndromes (FPLD) are rare diseases characterized by partial lack of subcutaneous fat resulting in a severe metabolic syndrome and cardiovascular complications. Besides premature cell senescence, 2 main mechanisms are involved in FPLD: impaired adipocyte differentiation and lipid droplet, corresponding to two of the main causes of FPLD: LMNA-related FPLD2 and PLIN-related FPLD4. The objective of this study was to compare the clinical, metabolic and immuno-hematological profile of these 2 types of FPLD.

Methods: The study was conducted in the frame of a prospective cohort (NCT0178428) aiming to characterize different types of fat disorders associated with a variable degree of insulin resistance from lean control subjects to obese patients and lipodystrophy syndromes in a university hospital. Clinical (sex, age), metabolic (HbA1c, fasting blood glucose and C-peptide, triglycerides, liver enzymes, leptin, CRP), % of fat mass (DEXA), intra&total abdominal fat and % of liver steatosis (MRI) were recorded. Four groups of patients (20 lean and 20 non-diabetic obese patients, 26 R482-LMNA-mutated patients and 8 PLIN1-linked FPLD patients were compared with the Mann-Whitney test, whereas correlation studies were done with the Pearson test.

Results: The 2 FPLD groups (FPLD2 and FPLD4) showed higher BMI, intraabdominal fat, HbA1c, triglycerides, ALAT, fatty liver, and eosinophils than the lean controls, but FPLD2 and FPLD4 groups only differed by a significantly lower leptin level in the FPLD4 group. Compared to lean controls, leukocytes & neutrophils were increased, and NK cells decreased, in the FPLD2 group. Basophils levels were increased in the FPLD4 group compared to lean, but also obese subjects. Basophils were the cell subtype the most often correlated positively with metabolic (HbA1c, FBG, triglycerides) and liver (ALAT, steatosis %) parameters, and negatively with the % of body fat mass and leptin `levels.

Conclusion: This is the first report comparing the clinical and biological phenotype, including immune-hematological profile, of FPLD patients, especially the rare FPLD4 patients, to lean and obese control groups. Although the controverses on the pathogenicity of PLIN1 variants, the phenotype of FPLD4 was similar to FPLD2, with however a less severe lipoatrophy as suggested by a lower leptin level. In addition, despite the small size of the groups, we found variations of NK and basophils cells, key cells involved in Th2 response, suggesting the potential interest of targeting basophil activation with treatments such as omalizumab, benlizumab, in the field of these rare orphan diseases.