Hypercholesterolemia management in a patient with mitochondrial encephalomyopathy lactic acidosis, and stroke-like episodes

Abstract

Background/Synopsis

Mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) is a rare, genetic neurodegenerative disorder caused by mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) Belal et al. (2022), Chakrabarty et al. (2021), and Cheng et al. (2022). MELAS can present with a wide range of symptoms, including stroke-like episodes, lactic acidosis, and multi-organ involvement. Statins are contraindicated in MELAS due to potentially exacerbating mitochondrial dysfunction via Coenzyme Q10 (CoQ10) depletion. Non-statin lipid lowering therapies in MELAS patients have appeared favorable.

Objective/Purpose

To highlight the challenges in hypercholesterolemia management with existing mitochondrial disorders and the potential of non-statin options.

Methods

Statins inhibit CoA reductase activity, which also affects the synthetic pathway of CoQ10 (Argov, 2024). CoQ10 is a component of normal mitochondrial function, and low levels of CoQ10 in muscle tissue have been found in statin associated myopathy (Lamperti et al., 2005). Two reported case studies describe a MELAS-like clinical syndrome that occurred after several months of statin therapy (Chariot et al., 1993; Tsivgoulis et al., 2006). Both developed rhabdomyolysis with elevated CK (20,000 U/L and 45,000-48,000 U/L, respectively). No mitochondrial DNA mutation was identified, yet the statin unmasked a subclinical mitochondrial muscle disease.

Research on use of non-statin therapies (ezetimibe and PCSK9 inhibitors) in patients with MELAS or mitochondrial disorders is limited. However, one case study in a patient with mitochondrial myopathy due to heteroplasmic mitochondrial DNA missence mutation in MTCO1 gene (m.7671T>A) demonstrated stable CK levels without recurrence of myalgia while taking alirocumab 75 mg every 2 weeks, ezetimibe 10 mg daily, marine omega 3 fatty acids daily, and 145 mg of micronized fenofibrate every 2 days (Cicero et al., 2020).

Results

A 48-year-old male presented with MELAS due to a mitochondrial mutation. He had a history of hypercholesterolemia with debilitating myalgias on simvastatin, atorvastatin and rosuvastatin prior to MELAS diagnosis. His baseline total cholesterol was 248 mg/dL, HDL 38 mg/dL, LDL-C 254 mg/dL, triglycerides 278 mg/dL, and non-HDL 310 mg/dL. Ezetimibe 10 mg daily and icosapent ethyl 4 g daily was initiated and well tolerated. His total cholesterol improved to 221 mg/dL, HDL 37 mg/dL, LDL-C 155 mg/dL, triglycerides 146 mg/dL, non-HDL 184 mg/dL. Evolocumab 140 mg subcutaneous every 14 days was prescribed and tolerated without side effects. His cholesterol further improved to 108 mg/dL, HDL 38 mg/dL, LDL-C 43 mg/dL, triglycerides 162 mg/dL, and non-HDL 70 mg/dL. AST and ALT remained normal throughout treatment.

Conclusions

This case highlights consideration for MELAS in young adults with stroke-like episodes and demonstrates successful use of non-statin lipid lowering medications to manage hypercholesterolemia. Further research is necessary in this patient population.