Phytosterolemia: A case of paradoxical hypercholesterolemia in response to a mediterranean diet

Background/Synopsis

Phytosterolemia is a rare autosomal recessive lipid disorder caused by variants of the sterol efflux transporter genes ABCG5 and ABCG8 leading to increased intestinal absorption and decreased hepatic elimination of plant sterols. Patients may be misdiagnosed with heterozygous familial hypercholesterolemia. Additionally, they may present with atypical responses to nutrition interventions recommended for atherosclerotic cardiovascular disease (ASCVD) prevention.

Objective/Purpose

To describe the clinical pathway of a patient who experienced increased total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels after adopting a Mediterranean dietary pattern and outline diagnostic testing and management strategies for a rare lipid disorder.

Methods

We present a case report.

Results

HT is a 54-year-old post-menopausal woman who presented to preventive cardiology clinic for consultation for hypercholesterolemia. Baseline TC was 256 mg/dL and LDL-C was 148 mg/dL. HT was physically active with no history of smoking. Family history was negative for premature ASCVD. On physical exam, she had a BMI of 22.49 kg/m², a normal cardiovascular exam, and no xanthomas were noted.

HT's 10-year ASCVD risk score indicated low-risk (1.1%). HT was encouraged to follow the Mediterranean dietary pattern (MedDiet) to address her elevated LDL-C levels. HT demonstrated good adherence and increased her intake of whole grains, legumes, nuts, avocados, and olive oil. Follow-up laboratory results at two months demonstrated TC increased to 317 mg/dL and LDL-C to 203 mg/dL (see Figure).

The atypical response to the MedDiet resulted in further diagnostic testing, which revealed a significantly elevated beta-sitosterol level of 11 mg/L (normal <5 mg/L) highly suggestive of phytosterolemia. HT was prescribed ezetimibe 10 mg, discontinued the MedDiet, and was educated on a low-plant sterol diet. After one month, TC was 193 mg/dL and LDL-C was 106 mg/dL. After 6 months on the treatment plan, TC decreased to 180 mg/dL, LDL-C decreased to 90 mg/dL, and beta-sitosterol decreased to 2.8 mg/L. She was encouraged to continue with the current therapeutic regimen and referred to a registered dietitian to assure optimal nutrition with a low-plant sterol diet

Conclusions

Though extremely rare, phytosterolemia should be considered in patients with hypercholesterolemia who have paradoxical responses to whole food, plant-based diets or those with early ASCVD without obvious etiology. In this patient, diagnosis was via laboratory assays that showed elevated plasma plant sterol levels, including beta-sitosterol. Variants of ABCG5 and ABCG8 genes can provide genetic confirmation. Lipid-lowering was achieved with a low-plant sterol diet and ezetimibe 10 mg.