Supplementary Material for: Clinical and Genetic Insights into Congenital Generalized Lipodystrophy Type 4: A Case Report

Introduction: Lipodystrophy syndromes (LS) represent a clinically and genetically diverse group of disorders characterised by a partial or generalised deficiency of adipose tissue. LS are characterised by a partial or generalised deficiency of adipose tissue, and variations in fat distribution throughout the body. Metabolic complications serve as significant determinants of morbidity and mortality in these syndromes.
Case Presentation: The patient was assessed for general lipodystrophy and myopathy findings, and a CAVIN1 mutation was identified by next-generation sequencing. Our patient exhibited low leptin and vitamin D levels, categorised as metabolic disorders, alongside increased insulin resistance. Additionally, low IGF-1 levels and delayed puberty were noted as hormonal disorders. Osteoporosis, scoliosis, ventricular extrasystoles, and ventricular tachycardia were observed as morbid conditions during the follow-up. We detected hypoplasia of the anterior cerebral artery and internal carotid artery, which are seen as ultra-rare. A coexistent structural cerebral vascular anomaly has not been previously reported in congenital generalized lipodystrophy type 4.
Conclusion: Congenital generalized lipodystrophy type 4 should be prioritised when associated with elevated liver enzyme levels and creatine phosphokinase (CPK) values. Determining the underlying genetic cause enables an expeditious monitoring and treatment process.

概述：脂肪营养不良综合征（Lipodystrophy Syndromes, LS）是一类临床与遗传特征均具有高度异质性的疾病群，以部分或全身性脂肪组织缺失为核心特征，同时可伴随全身脂肪分布异常。代谢并发症是此类综合征患者发病率与死亡率的重要影响因素。

病例报告：本研究针对患者的全身性脂肪营养不良与肌病表现开展评估，并通过下一代测序（next-generation sequencing, NGS）检出CAVIN1基因突变。患者表现为瘦素与维生素D水平降低，属于代谢紊乱范畴，同时伴随胰岛素抵抗加重；此外还存在胰岛素样生长因子1（Insulin-like Growth Factor 1, IGF-1）水平降低与青春期延迟，属于内分泌紊乱范畴。随访期间还观察到骨质疏松、脊柱侧凸、室性期前收缩与室性心动过速等病症。本次研究检出患者存在大脑前动脉与颈内动脉发育不全，此类表现极为罕见。目前尚无先天性全身性脂肪营养不良4型（Congenital Generalized Lipodystrophy Type 4, CGL4）合并此类脑血管结构异常的相关报道。

结论：当先天性全身性脂肪营养不良4型患者出现肝酶与肌酸磷酸激酶（Creatine Phosphokinase, CPK）水平升高时，应将其列为重点关注对象。明确潜在的遗传学病因，可助力实现快速的病情监测与治疗干预。