Clinical and Molecular Prevalence of Lipodystrophy in an Unascertained Large Clinical Care Cohort.

Lipodystrophies are a group of disorders characterized by absence or loss of adipose tissue and abnormal fat distribution, commonly accompanied by metabolic dysregulation. Although considered rare disorders, their prevalence in the general population is not well understood. We aimed to evaluate the clinical and genetic prevalence of lipodystrophy disorders in a large clinical care cohort. We interrogated the electronic health record (EHR) information of >1.3 million adults from the Geisinger Health System for lipodystrophy diagnostic codes. We estimate a clinical prevalence of disease of 1 in 20,000 individuals. We performed genetic analyses in individuals with available genomic data to identify variants associated with inherited lipodystrophies and examined their EHR for comorbidities associated with lipodystrophy. We identified 16 individuals carrying the p.R482Q pathogenic variant in LMNA associated with Dunnigan familial partial lipodystrophy. Four had a clinical diagnosis of lipodystrophy, whereas the remaining had no documented clinical diagnosis despite having accompanying metabolic abnormalities. We observed a lipodystrophy-associated variant carrier frequency of 1 in 3,082 individuals in our cohort with substantial burden of metabolic dysregulation. We estimate a genetic prevalence of disease of ∼1 in 7,000 in the general population. Partial lipodystrophy is an underdiagnosed condition. and its prevalence, as defined molecularly, is higher than previously reported. Genetically guided stratification of patients with common metabolic disorders, like diabetes and dyslipidemia, is an important step toward precision medicine.

Gonzaga-Jauregui C ，Ge W ，Staples J ，Van Hout C ，Yadav A ，Colonie R ，Leader JB ，Kirchner HL ，Murray MF ，Reid JG ，Carey DJ ，Overton JD ，Shuldiner AR ，Gottesman O ，Gao S ，Gromada J ，Baras A ，Altarejos J ，Geisinger-Regeneron DiscovEHR collaboration ... -  《-》

Deciphering the Clinical Presentations in LMNA-related Lipodystrophy: Report of 115 Cases and a Systematic Review.

Besci O ，Foss de Freitas MC ，Guidorizzi NR ，Guler MC ，Gilio D ，Maung JN ，Schill RL ，Hoose KS ，Obua BN ，Gomes AD ，Yıldırım Şimşir I ，Demir K ，Akinci B ，MacDougald OA ，Oral EA ... -  《-》

Mesangiocapillary glomerulonephritis type 2 associated with familial partial lipodystrophy (Dunnigan-Kobberling syndrome).

The lipodystrophies are a heterogeneous group of disorders of adipose tissue associated with insulin resistance. The sporadic form of partial lipodystrophy, characterised by fat loss from the face and upper body, is associated with complement abnormalities and mesangiocapillary glomerulonephritis type 2 (MCGN II) and the conditions are thought to have a shared autoimmune aetiology. We present the first case of the rare familial form of partial lipodystrophy, caused by a mutation in the LMNA gene, associated with MCGN II. This suggests that partial lipodystrophy of both the sporadic and familial subtypes may predispose to this condition and that the observed renal and complement abnormalities may be secondary to other factors associated with lipodystrophy.

Owen KR ，Donohoe M ，Ellard S ，Clarke TJ ，Nicholls AJ ，Hattersley AT ，Bingham C ... -  《nephron clinical practice》

Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations.

Mory PB ，Crispim F ，Freire MB ，Salles JE ，Valério CM ，Godoy-Matos AF ，Dib SA ，Moisés RS ... -  《-》

Prevalence of clinical characteristics of lipodystrophy in the US adult population in a healthcare claims database.

Lipodystrophy is characterized by progressive loss of adipose tissue and consequential metabolic abnormalities. With new treatments emerging for lipodystrophy, there is a growing need to understand the prevalence of specific comorbidities that may be commonly associated with lipodystrophy to contextualize the natural history of lipodystrophy without any disease modifying therapy. To examine the risk of specific clinical characteristics in people living with lipodystrophy (LD) in 2018-2019 compared with the general US population, among the commercially insured US population. A retrospective cohort study was conducted using the 2018-2019 Clinformatics® Data Mart database. An adult LD cohort (age ≥ 18 years) with at least ≥ 1 inpatient or ≥ 2 outpatient LD diagnoses was created. The LD cohort included non-HIV-associated LD (non-HIV-LD) and HIV-associated LD (HIV-LD) subgroups and compared against age- and sex-matched control groups with a 1:4 ratio from the general population with neither an LD or an HIV diagnosis using odds ratios (ORs) with 95% confidence intervals. We identified 546 individuals with non-HIV-LD (mean age, 60.3 ± 14.9 years; female, 67.6%) and 334 individuals with HIV-LD (mean age, 59.2 ± 8.3 years; female, 15.0%) in 2018-2019. Compared with the general population, individuals with non-HIV-LD had higher risks (odds ratio [95% confidence interval]) for hyperlipidemia (3.32 [2.71-4.09]), hypertension (3.58 [2.89-4.44]), diabetes mellitus (4.72 [3.85-5.79]), kidney disease (2.78 [2.19-3.53]), liver fibrosis or cirrhosis (4.06 [1.66-9.95]), cancer (2.20 [1.59-3.01]), and serious infections resulting in hospitalization (3.00 [2.19-4.10]). Compared with individuals with HIV, those with HIV-LD have higher odds of hypertension (1.47 [1.13-1.92]), hyperlipidemia (2.46 [1.86-3.28]), and diabetes (1.37 [1.04-1.79]). LD imposes a substantial burden on affected individuals due to a high prevalence of metabolic comorbidities and other complications as compared with the general non-LD population. Future longitudinal follow-up studies investigating the causality between LD and observed comorbidities are warranted.

Yang S ，Knox C 《BMC Endocrine Disorders》