Study Of Clinical Manifestation And Biomolecular Genetics In Lipodystrophic Patients

ObjectiveLipodystrophic syndrome is a rare disease characterized by adipose tissue loss and severe metabolic disorder.The pattern and severity of fat loss in different subtypes of lipodystrophy varies from each other.The published articles described the characteristics of fat distribution roughly,which usually was limited in the level of trunk and limbs,without further details.Therefore,it is difficult to classify the subtypes of lipodystrophy by clinical manifestations,especially the fat patterns.In addition,the genetics of lipodystrophy is complicated due to the great variety of pathogenic genes,which makes it a big challenge in choosing the list of genes to detect for further confirming diagnosis.Studies showed leptin and adiponectin played important roles in the development of lipodystrophy.However,the above two adipokines were under-emphasized and relevant data was lack in most published articles.The prevalence of lipodystrophy is low and no sufficient information is reported.The poor understanding of lipodystrophy becomes a barrier to provide effective and timely treatment for the patients,which lowers their life quality.We aim to explore the underlying secrete of lipodystrophy by investigating the clinical phenotypes and biomolecular genetics of five patients,so that we may find a better way to deal with the disease.MethodClinical informat ion of five patients with lipodystrophy admitted to Peking Union Medical College Hospital from January 2015 to February 2017 was colected.The regular laboratory tests related to metabolism and the levels of leptin and adiponectin were determined and the subsequent diffuse weight imaging and quantitative computed tomography were conducted to quantify the adipose tissue.Whole-exome sequencing was carried out and advanced data analysis and literature review were done to detect the possible causative mutated gene and thoir·pathogenic mechanism.ResultClinical information and result of imaging study showed five patients presented different extents and severities of adipose tissue atrophy and four of them also suffered from selective fat accumulation.All the patients developed stubborn insulin resistance and hyperlipidemia,accompanied with significant decrease in the level of leptin and adiponectin.The result of whole-exome sequencing and data analysis revealed that Patient L2 and L5 had pathogenic mutated LMNA(p.R482W and p.R349W,respectively)and mutated PLIN1(p.P194A)with uncertain pathogenic significance.The clinical manifestation of Patient L4 met the characteristics of familial partial lipodystrophic disease type 1.Most patients responded better to thiazolidinedione than other most oral hypoglycemic agents in treating glucose metabolic disorder in lipodystrophy.ConclusionCongenital lipodystrophy is very complicated for its varieties of phenotypes and causative genes and there are some underwater genes related to the disease.Congenital lipodystrophy may be a consequence of co-reaction between multiple genes.It is essential to build the database of clinical phenotypes of lipodystrophic diseases to help early clinical diagnosis and treatment.Individual treatment based on understanding the pathogenic mechanism is necessary to overcome the disease.