Fountas Athanasios, Giotaki Zoe, Dounousi Evangelia, Liapis George, Bargiota Alexandra, Tsatsoulis Agathocles, Tigas Stelios
Departments of Endocrinology.
Nephrology, University Hospital of Ioannina, IoanninaGreece.
Endocrinol Diabetes Metab Case Rep. 2017 Jun 2;2017. doi: 10.1530/EDM-17-0049. eCollection 2017.
Proteinuric renal disease is prevalent in congenital or acquired forms of generalized lipodystrophy. In contrast, an association between familial partial lipodystrophy (FPLD) and renal disease has been documented in very few cases. A 22-year-old female patient presented with impaired glucose tolerance, hyperinsulinemia, hirsutism and oligomenorrhea. On examination, there was partial loss of subcutaneous adipose tissue in the face, upper and lower limbs, bird-like facies with micrognathia and low set ears and mild acanthosis nigricans. Laboratory investigations revealed hyperandrogenism, hyperlipidemia, elevated serum creatine kinase and mild proteinuria. A clinical diagnosis of FPLD of the non-Dunnigan variety was made; genetic testing revealed a heterozygous c.1045C > T mutation in exon 6 of the gene, predicted to result in an abnormal LMNA protein (p.R349W). Electromyography and muscle biopsy were suggestive of non-specific myopathy. Treatment with metformin and later with pioglitazone was initiated. Due to worsening proteinuria, a renal biopsy was performed; histological findings were consistent with mild focal glomerular mesangioproliferative changes, and the patient was started on angiotensin-converting enzyme inhibitor therapy. This is the fourth report of FPLD associated with the c.1045C > T missense mutation and the second with co-existent proteinuric renal disease. Patients carrying this specific mutation may exhibit a phenotype that includes partial lipodystrophy, proteinuric nephropathy, cardiomyopathy and atypical myopathy.
Lipodystrophy is a rare disorder characterized by the complete or partial loss of subcutaneous adipose tissue, insulin resistance, diabetes mellitus and hyperlipidemia.Proteinuric renal disease is a prevalent feature of generalized lipodystrophy but rare in familial partial lipodystrophy.Patients carrying the c.1045C > T missense mutation (p.R349W) may present with familial partial lipodystrophy, proteinuric nephropathy, cardiomyopathy and atypical myopathy.
蛋白尿性肾病在先天性或获得性全身性脂肪营养不良中很常见。相比之下，家族性部分性脂肪营养不良（FPLD）与肾病之间的关联仅在极少数病例中有记录。一名22岁女性患者出现糖耐量受损、高胰岛素血症、多毛症和月经过少。检查发现面部、上肢和下肢皮下脂肪组织部分缺失，呈鸟样面容，伴有小颌畸形和低位耳，以及轻度黑棘皮病。实验室检查显示雄激素过多、高脂血症、血清肌酸激酶升高和轻度蛋白尿。临床诊断为非邓尼根型FPLD；基因检测显示该基因外显子6存在杂合性c.1045C＞T突变，预计会导致异常的LMNA蛋白（p.R349W）。肌电图和肌肉活检提示为非特异性肌病。开始用二甲双胍治疗，后来用吡格列酮治疗。由于蛋白尿恶化，进行了肾活检；组织学结果与轻度局灶性肾小球系膜增生性改变一致，患者开始接受血管紧张素转换酶抑制剂治疗。这是第四例与c.1045C＞T错义突变相关的FPLD报告，也是第二例伴有蛋白尿性肾病的报告。携带这种特定突变的患者可能表现出包括部分性脂肪营养不良、蛋白尿性肾病、心肌病和非典型肌病在内的表型。
脂肪营养不良是一种罕见的疾病，其特征是皮下脂肪组织完全或部分缺失、胰岛素抵抗、糖尿病和高脂血症。蛋白尿性肾病是全身性脂肪营养不良的常见特征，但在家族性部分性脂肪营养不良中罕见。携带c.1045C＞T错义突变（p.R349W）的患者可能表现出家族性部分性脂肪营养不良、蛋白尿性肾病、心肌病和非典型肌病。
