Besci Ozge, Foss de Freitas Maria Christina, Guidorizzi Natália Rossin, Guler Merve Celik, Gilio Donatella, Maung Jessica N, Schill Rebecca L, Hoose Keegan S, Obua Bonje N, Gomes Anabela D, Yıldırım Şimşir Ilgın, Demir Korcan, Akinci Baris, MacDougald Ormond A, Oral Elif A
Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, MI 48109, USA.
Division of Pediatric Endocrinology, Dokuz Eylul University, Izmir 35340, Turkey.
J Clin Endocrinol Metab. 2024 Feb 20;109(3):e1204-e1224. doi: 10.1210/clinem/dgad606.
Lipodystrophy syndromes are a heterogeneous group of rare genetic or acquired disorders characterized by generalized or partial loss of adipose tissue. LMNA-related lipodystrophy syndromes are classified based on the severity and distribution of adipose tissue loss.
We aimed to annotate all clinical and metabolic features of patients with lipodystrophy syndromes carrying pathogenic LMNA variants and assess potential genotype-phenotype relationships.
We retrospectively reviewed and analyzed all our cases (n = 115) and all published cases (n = 379) curated from 94 studies in the literature.
The study included 494 patients. The most common variants in our study, R482Q and R482W, were associated with similar metabolic characteristics and complications though those with the R482W variant were younger (aged 33 [24] years vs 44 [25] years; P < .001), had an earlier diabetes diagnosis (aged 27 [18] vs 40 [17] years; P < .001) and had lower body mass index levels (24 [5] vs 25 [4]; P = .037). Dyslipidemia was the earliest biochemical evidence described in 83% of all patients at a median age of 26 (10) years, while diabetes was reported in 61% of cases. Among 39 patients with an episode of acute pancreatitis, the median age at acute pancreatitis diagnosis was 20 (17) years. Patients who were reported to have diabetes had 3.2 times, while those with hypertriglyceridemia had 12.0 times, the odds of having pancreatitis compared to those who did not.
This study reports the largest number of patients with LMNA-related lipodystrophy syndromes to date. Our report helps to quantify the prevalence of the known and rare complications associated with different phenotypes and serves as a comprehensive catalog of all known cases.
脂肪营养不良综合征是一组异质性的罕见遗传或获得性疾病，其特征为全身或部分脂肪组织丢失。与LMNA相关的脂肪营养不良综合征根据脂肪组织丢失的严重程度和分布进行分类。
我们旨在阐明携带致病性LMNA变异的脂肪营养不良综合征患者的所有临床和代谢特征，并评估潜在的基因型-表型关系。
我们回顾性分析了我们所有的病例（n = 115）以及从94项文献研究中整理出的所有已发表病例（n = 379）。
该研究纳入了494例患者。我们研究中最常见的变异R482Q和R482W与相似的代谢特征和并发症相关，不过携带R482W变异的患者更年轻（年龄33 [24]岁对44 [25]岁；P <.001），糖尿病诊断更早（年龄27 [18]岁对40 [17]岁；P <.001），且体重指数水平更低（24 [5]对25 [4]；P =.037）。血脂异常是在所有患者中最早出现的生化证据，83%的患者在中位年龄26（10）岁时出现，而61%的病例报告有糖尿病。在39例急性胰腺炎发作的患者中，急性胰腺炎诊断时的中位年龄为20（17）岁。报告患有糖尿病的患者患胰腺炎的几率是未患糖尿病患者的3.2倍，而患有高甘油三酯血症的患者患胰腺炎的几率是未患高甘油三酯血症患者的12.0倍。
本研究报告了迄今为止数量最多的与LMNA相关的脂肪营养不良综合征患者。我们的报告有助于量化与不同表型相关的已知和罕见并发症的患病率，并作为所有已知病例的综合目录。
