Severe Atherogenic Dyslipidemia in Ataxia-Telangiectasia Despite Cachexia: Mechanistic Insights into Mitochondrial Dysfunction

Ataxia-telangiectasia is a rare autosomal recessive disorder caused by mutations in the ATM gene and characterized by progressive cerebellar degeneration, immunodeficiency, and cancer susceptibility. Metabolic complications, including dyslipidemia and insulin resistance, are increasingly recognized, but severe atherogenic lipid phenotypes remain poorly described. ATM deficiency impairs mitochondrial function, redox homeostasis, and fatty acid beta oxidation, providing a plausible basis for metabolic dysregulation. We report a 25-year-old woman with genetically confirmed ataxia-telangiectasia and extreme underweight (body mass index 12.5 kg/m²) who developed severe mixed atherogenic dyslipidemia despite modest dietary fat intake and no pathogenic variants causing monogenic familial hypercholesterolemia. Fasting triglycerides rose from 264 to 426 mg/dL, low-density lipoprotein cholesterol reached 174 mg/dL, apolipoprotein B was 156 mg/dL, lipoprotein a was 87 mg/dL, low-density lipoprotein particle number exceeded 3500 nmol/L, and small, dense low-density lipoprotein exceeded 2300 nmol/L. Concurrent diagnoses included type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease with fibrosis. Statin therapy was discontinued after elevated transaminases were noted in the setting of preexisting liver disease. Ezetimibe lowered low-density lipoprotein cholesterol from 174 to 149 mg/dL. After evolocumab was added to ezetimibe, low-density lipoprotein cholesterol decreased from 149 to 35 mg/dL, with triglycerides improving to 220 mg/dL and glycated hemoglobin A1c to 5.9%. This case expands the metabolic phenotype of ataxia-telangiectasia and supports careful cardiometabolic surveillance in affected adults.