Abstract Body (Do not enter title and authors here): Background
Familial partial lipodystrophy (FPLD) is a rare genetic disorder often underrecognized in clinical practice. Given its phenotypic overlap with common metabolic disorders, its identification as an underlying clinical syndrome is often delayed.
Case
A 41-year-old woman with type 1 diabetes mellitus (diagnosed following acute pancreatitis at age 19), necrobiosis lipoidica, combined hyperlipidemia, and prior triglyceride levels >1,000 mg/dL presented to the care with progressive exertional dyspnea. Physical examination revealed increased facial and nuchal adiposity with thin extremities featuring prominent veins, suggesting abnormal fat distribution. She had a recent marked improvement in her metabolic control (A1c down to 7.0% from 14.5%; triglycerides down to 112 mg/dL from 1160mg/dL) found to have NT-proBNP of 6,489 pg/mL and mildly elevated high-sensitivity troponin. Echocardiography revealed an LVEF of 38% with new regional wall motion abnormalities as well as grade 2 diastolic dysfunction. Invasive hemodynamics testing was notable for elevated bi-atrial filling pressures and subsequent coronary angiography revealed multivessel coronary artery disease.
Given the patient's selective fat loss, early-onset insulin-resistant diabetes, prior hypertriglyceridemia, and now premature cardiovascular disease leading to an ischemic cardiomyopathy, a unifying diagnosis of lipodystrophy was suspected. Genetic testing confirmed a pathogenic LMNA variant, consistent with type 2 familial partial lipodystrophy, also known as Dunnigan type.
Discussion
This case underscores the importance of pattern recognition in patients with atypical cardiometabolic profiles. The diagnosis of FPLD helped clarify the etiology of this patient’s cardiomyopathy and provided insight into her prior metabolic derangements. Early identification of LMNA mutations is crucial due to associated risks of arrhythmias, worsening cardiomyopathies, and sudden cardiac death. It also provided the patient with an explanation for her body morphology and the severity of her metabolic conditions, which she reported has reduced her body shame and enabled her to cope with her condition better.
Conclusion
Familial partial lipodystrophy should be considered in individuals with abnormal fat distribution, severe dyslipidemia, insulin resistance, and premature cardiovascular disease. Timely genetic testing can guide management and provide answers for patients who have delays in diagnosis.