Attrition of adipose: Type 2 familial partial lipodystrophy manifesting in severe premature CAD

Abstract

Background/Synopsis

Lipodystrophy constitutes a heterogeneous group of rare acquired or inherited conditions characterized by adipose tissue deficiency, typically manifesting in hypertriglyceridemia, insulin resistance, hyperglycemia, and fatty liver. Type 2 Familial Partial Lipodystrophy (FPLD2), also known as Dunnigan variant, is an autosomal dominant disorder with onset around puberty characterized by absence of adiposity in limbs and trunk with increased face and neck fat deposition, sometimes associated with skeletal muscle hypertrophy and phlebomegaly. Here, we describe a patient with history of severe hypertriglyceridemia (HTG) and type 1 diabetes (T1DM) who developed premature multivessel coronary artery disease (CAD) and ischemic cardiomyopathy, ultimately diagnosed with FPLD2.

Objective/Purpose

Not applicable to this case study abstract submission.

Methods

Case study.

Results

LD is a 41-year-old female with newly diagnosed ischemic cardiomyopathy (EF 38%), triple-vessel CAD status-post drug-eluting stent to mid-LAD, severe HTG complicated by recurrent acute pancreatitis, and T1DM. Since childhood, LD reported insatiable appetite despite a thin, muscular frame disproportionate to normal activity. At 19, she was diagnosed simultaneously with T1DM, acute pancreatitis, and severe HTG. Family history was notable for a maternal aunt with similar body morphology and metabolic disease. At evaluation, her only complaint was persistent hunger, though less intense than during early adulthood. Hgb A1C was 7.0% on a continuous insulin pump at 1U/hr requiring minimal bolus dosing for meals. Physical exam was notable for absence of abdominal adiposity below the upper chest with sparing of the head and neck, muscular calf muscles, and prominent peripheral veins, consistent with FPLD2. Figure 1 reports lipid panel on high-intensity statin. She had normal serum creatinine, transaminase levels, thyroid stimulating hormone, and urine albumin-creatinine ratio. She was prescribed icosapent ethyl and introduced to a lipodystrophy patient advocacy group. Fasting leptin and genetic testing were ordered, but not completed.

Conclusions

Lipodystrophy is a clinical diagnosis based on physical exam, family and personal history, and metabolic features of insulin resistance and may be supported by genetic testing. Based on LD's adipose distribution, dyslipidemia, and family history, FPLD2 was diagnosed. Initial management involves targeting insulin resistance and treatment of comorbid sequelae. Metreleptin (recombinant leptin analog) is approved for severe generalized lipodystrophy and under investigation for partial lipodystrophy, while a similar leptin receptor agonist trial was terminated. LD expressed gratitude that knowing her diagnosis and connecting with others made her feel less alone and more supported. This case highlights the importance of considering lipodystrophy in the differential diagnosis of patients presenting with atypical features of classical metabolic syndrome and suggestive adipose distribution.