Familial partial lipodystrophy:genetic and clinical data from a greek referral center

Aikaterini Kountouri; Emmanouil Korakas; Eirini Maratou; Ignatios Ikonomidis; Konstantinos Balampanis; Loukia Pliouta; Stavros Liatis; Nikolaos Tentolouris; Panagiotis Toulas; Foteini Kousathana; Christoforos Giatzakis; George Dimitriadis; Vaia Lambadiari

doi:10.1530/endoabs.99.P261

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Endocrine Abstracts (2024) 99 P261 | DOI: 10.1530/endoabs.99.P261

ECE2024 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (130 abstracts)

Familial partial lipodystrophy:genetic and clinical data from a greek referral center

Aikaterini Kountouri ¹ , Emmanouil Korakas ¹ , Eirini Maratou ² , Ignatios Ikonomidis ³ , Konstantinos Balampanis ¹ , Loukia Pliouta ¹ , Stavros Liatis ⁴ , Nikolaos Tentolouris ⁴ , Panagiotis Toulas ⁵ , Foteini Kousathana ¹ , Christoforos Giatzakis ⁶ , George Dimitriadis ⁷ & Vaia Lambadiari ¹

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Author affiliations

¹Attikon University Hospital, Second Department of Internal Medicine, Chaidari, Greece; ²Attikon University Hospital, Department of Clinical Biochemistry, Chaidari, Greece; ³Attikon University Hospital, Second Cardiology Department, Chaidari, Greece; ⁴Laiko Hospital, First Department of Propaedeutic and Internal Medicine, Athens, Greece; ⁵Bioiatriki Healthcare Group, Athens, Greece; ⁶DNAbiolab, Cretan Center for Research and Development of Applications on Genetics and Molecular Biology, Heraklion, Greece; ⁷Sector of Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece

Background: Familial partial lipodystrophy (FPLD) is a rare syndrome in which a patient’s phenotype is not dependent merely on the specific genetic mutation, but also on a combination of other demographic, environmental and genetic factors. In this report, we present a large cohort of novel mutation in FPLD patients from a large referral center in Greece and we investigate the possible relationship between the genetic variations detected and their phenotype and the effect of metreleptin treatment in eligible FPLD patients.

Methods: This is a prospective observational study in a Greek referral center, included patients who fulfilled the clinical criteria of FPLD. A genetic analysis was conducted, which included sequence and deletion/duplication analyses of the LMNA and PPRARG genes. Anthropometric parameters and laboratory examinations were evaluated. The treatment responses of patients who received treatment with metreleptin were evaluated at 3 and 12 months.

Results: Overall, 39 patients were included in the study. The mean±SD age was 47.59±10.13 years, and 30 patients were female (76.9%). All the patients presented lipoatrophy in lower limbs, 59% in upper limbs and 66.7% in gluteal area. 97.4% displayed fat deposition in the abdomen, 46.2% in the trunk, 56.4% in the face and 35.9% in the neck. 76.9% presented acanthosis nigricans while 12.8% displayed muscular hypertrophy. Regarding the comorbidities related to lipodystrophy phenotype, 66.7% suffered from diabetes mellitus, thirty 76.9% presented dyslipidemia, 61.5% had hypertension, 56.4% had NASH or NAFLD and six 5.4% suffered from heart diseases. 33.3% of females met the criteria for PCOS. Genetic testing for did not result in any of the already known pathogenic mutations, but it revealed three likely pathogenic mutations, along with various changes in other exons and introns, especially in introns 7 and 10, whose pathogenicity and the subsequent role in the patients’ phenotype remains unclear. Treatment with metreleptin in eligible FPLD patients significantly improved indices of glycemic and lipidemic control, and the benefit was sustained after 12 months.

Conclusion: We have shown the presence of mutations both in exons, which are different from the ones which already have an established association with the disease, and in introns, which might also contribute to the final amino acid products and the phenotype of the patient. The sustainable and favorable results of metreleptin treatment in FPLD patients were confirmed, and they are independent from any baseline parameters.