6889 Potential Impact of Parental Origin of Inheritance in Presentation of Familial Partial Lipodystrophy
Authors: Gilio D , Foss de Freitas M C , Besci O , Guler M Celik , Neidert A , Yildirim I , Akinci B , Oral E A 
Published: October 2024

Disclosure: D. Gilio: None. M.C. Foss de Freitas: Advisory Board Member; Self; PTC Therapeutics. Speaker; Self; Amryt. O. Besci: None. M. Celik Guler: None. A. Neidert: None. I. Yildirim: None. B. Akinci: Advisory Board Member; Self; Amryt. Consulting Fee; Self; Regeneron Pharmaceuticals, Alnylam Pharmaceuticals, Amryt, AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novartis Pharmaceuticals, Novo Nordisk, Sanofi-Aventis, Servier, Third Rock Ventures. E.A. Oral: Advisory Board Member; Self; Amryt, Regeneron Pharmaceuticals. Consulting Fee; Self; Regeneron Pharmaceuticals, Amryt, Third Rock Ventures. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt. Research Investigator; Self; Novo Nordisk, Fractyl, Ionis Pharmaceuticals Inc., GI Dynamics, Rhythm Pharmaceuticals. Other; Self; Amryt.

Background: Familial partial lipodystrophy Type 2 (FPLD2) caused by autosomal dominant LMNA variants is characterized by partial loss of subcutaneous adipose tissue in the limbs, trunk, and gluteal region with accumulation in other parts of the body, such as the face and neck. It is usually associated with different degrees of insulin resistance and hypertriglyceridemia and body composition patterns. We wanted to know the contributing factors for the different metabolic abnormalities and body composition presentations of FPLD2. We hypothesized that parental inheritance line may be a contributory factor to the expression of the metabolic phenotype and body composition characteristics. Methods: We retrospectively collected clinical data of 77 FPLD2 cases from the Divisions of Metabolism and Endocrinology of 3 different sites: the University of Michigan, the University of São Paulo and The Turkish Lipodystrophy Study Group (TuLip). We further selected 53 published cases curated from 15 studies in the literature. For inclusion of the studies, we used web search tools including PubMed, OMIM and Google Scholar. Only patients where we could assess the genetic inheritance were included in this study. Data collected included demographic information, medical history and laboratory results. Results: 79 patients inherited the LMNA variant from the mother (Group 1; 18 males and 61 females), and 51 patients inherited it from the father (Group 2; 14 males and 37 females). The median age at lipodystrophy diagnosis was lower in Group 1 than in Group 2. Diabetes was reported in more than half of the groups; however, the prevalence rates were not significantly different. The mean age (± SEM) at first diagnosis of diabetes was 30 ± 15 years in Group 1 and 32 ± 11 years in Group 2; the microvascular complications were present in 8 patients with diabetes in Group 1 (36.3%) and in 5 patients in Group 2 (23.8%). Both groups' mean triglycerides levels were &gt;150 mg/dL, with a trend of higher triglycerides in Group 2 than in Group 1. Episodes of acute pancreatitis were identified in 9 patients (19.5%) of Group 1 and 10 patients (31.2%) of Group 2; however, patients in Group 1 showed 1.7 episodes of pancreatitis per person while Group 2 showed 8.1 episodes per person on average. The fatty liver disease was the most common liver abnormality identified and it seemed to be more frequent in Group 2 than in Group 1. There was no difference between the two groups in relation to the body mass index (BMI) and the ratio of percent fat mass of the trunk to percent fat mass of the legs (FMR); however, the DEXA (dual x-ray absorptiometry) showed a higher total fat mass in Group 1 compared to Group 2 (22.2 versus 17.3 Kg, p=0.040) in the presence of comparable total lean mass. Conclusion: Our data suggest that there is a difference in body fat mass according to the genetic inheritance, however the metabolic impact is not completely clear and require more detailed analysis.

Presentation: 6/1/2024