A case of dysbetalipoproteinemia: diagnostic and therapeutic strategies

Background/Synopsis

Dysbetalipoproteinemia (DBL) is an underdiagnosed inherited disorder of remnant lipoprotein metabolism associated with high levels of cholesterol and triglycerides (TG). In DBL, dysfunctional apolipoprotein E (apoE) impairs LDL receptor-mediated clearance of apoB-containing lipoproteins.   

Objective/Purpose

Describe a case with dysbetalipoproteinemia including diagnosis, management and treatment. Highlight the role of specialty lipid clinics in optimizing care for patients with uncommon lipid disorders. 

Methods

Case report about dysbetalipoproteinemia.

Results

A 40-year-old male with a history of hypertension, pre-diabetes, and obesity (BMI 32) first learned he had high cholesterol in his 20s. His mother and 15-year-old son also have elevated cholesterol. He smokes four to five cigarettes intermittently and drinks two to three beers monthly.

The patient's baseline lipid values showed TG 582 mg/dL, non-HDL-cholesterol (non-HDL-C) 365 mg/dL, total cholesterol (TC) 403 mg/dL. Atorvastatin 80 mg was initiated with subsequent labs noting TG 358 mg/dL, LDL 174.3 mg/dL (Martin-Hopkins method), apoB 85 mg/dL, TC 275 mg/dL, HDL 40 mg/dL. Lp(a) was within normal limits. 

He returned to the clinic three years later, off lipid lowering therapy (LLT), complaining of firm, yellow nodules at the elbows. Labs revealed TG 764 mg/dL, non-HDL-C 515 mg/dL, TC 548 mg/dL. Atorvastatin 80 mg, non-prescribed omega-3 fatty acid 1 gram, and fenofibrate 48 mg were initiated. Biopsy confirmed xanthomas, which prompted referral to lipid clinic. 

In lipid clinic, discordance between LDL-C and apoB raised suspicion for dysbetalipoproteinemia. Genetic testing  demonstrated homozygosity for the APOE2 allele and heterozygosity for a risk variant in the APOA5 gene, consistent with familial dysbetalipoproteinemia. A non-contrast CT coronary returned with a calcium score of 38, placing him in the 93rd percentile based on age/sex. Omega-3 supplement was discontinued, and ezetimibe was added to LLT. Repeat labs demonstrated TG 340 mg/dL, non-HDL-C 149 mg/dL.  Lifestyle counseling was provided, fenofibrate discontinued. Further LDL-C/apoB lowering is being considered. 

Conclusions

Patients with suspected DBL should be seen expeditiously in specialty lipid clinics to manage lipid levels and long-term cardiovascular risk. Dysbetalipoproteinemia should be considered in patients with elevated levels of cholesterol and TG, especially if xanthomas are present. Diagnosis is supported by normal or mildly elevated apoB levels. If genetic testing confirms APOE2 homozygosity, a secondary metabolic “hit” is still needed to express DBL phenotype. Treatment of DBL focuses on lifestyle modifications, including a traditional type III diet, alcohol limitation, exercise, and weight loss. LLT should be initiated when lifestyle modifications are insufficient.