P200 - ECE_1716 - Longitudinal clinical and metabolic profile of male patients with LMNA-related lipodystrophy syndromes
TL;DR
The phenotypic diversity of laminopathies in men is confirmed and the need for repeated cardiometabolic evaluation and diabetes screening regardless of the pathogenic variant is highlighted.
Abstract
Laminopathies are rare disorders caused by variants in the LMNA gene. They display clinical heterogeneity, ranging from frequent forms of partial lipodystrophy (FPLD2) with diabetes to rarer cardiac or muscular forms. A female predominance is observed in FPLD2 due to a phenotype easier to identify with severe metabolic complications. Diagnosis in male subjects is more challenging, and the disease course has been poorly studied. To describe the clinical and metabolic follow-up of male subjects carrying a pathogenic LMNA variant and to compare carriers of the R482-LMNA mutation associated with FPLD2, with carriers of other LMNA variants. This retrospective, single-center cohort included 33 LMNA-mutated men (median age at V1 42(28-51); BMI 25(23-28)) who were followed for a mean duration of 8 years in a referral centre. Clinical, biological and anthropometric (assessed with metabolic MRI & DEXA) data were compared between the first (V1) & the last visit (V2), and between the R482-LMNA carriers (n = 10) and those carrying other variants (non-R482 group, n = 23). During the follow-up, in the treated whole group, a significant decrease in triglyceride, alanine aminotransferase, leptin, intra- and total abdominal fat was observed, along with a trend toward improvement in insulin-resistance parameters and femoral Z-score. At V1, R482 carriers exhibited more metabolic complications (higher blood pressure, HbA1c, liver steatosis, intra/total abdominal fat ratio, & lower leptin levels) than non-R482 patients, who presented with cardiac complications (implantable cardiac device (ICD), heart failure) in 40% of cases vs 0% in the R482 group. Longitudinal analysis nevertheless revealed a substantial incidence of diabetes in the non-R482 group and a significant increase in ICD in the R482 group. This study confirms the phenotypic diversity of laminopathies in men and highlights the need for repeated cardiometabolic evaluation and diabetes screening regardless of the pathogenic variant.