A Case of Hypolipidemia and Hypocholesterolemia; Cause and Consequences

Background: Hypolipidemia and hypocholesterolemia are uncommon and because of the established risk of hypercholesterolemia for cardiovascular disease, reduced lipids and total cholesterol levels are often clinically desired and/or deemed clinically inconsequential. A finding of persistently low lipid levels and total cholesterol may however not be innocuous nor desirable. We describe the case of a 46 yr old man with persistently low total cholesterol levels <70mg/dl and the associated complications and comorbidities identified. Clinical Case: A 46 yr old Hispanic man with non-alcoholic fatty liver disease (NAFLD) was referred for evaluation of hyperhidrosis in the setting of persistent hypolipidemia and hypocholesterolemia. Review of the patient’s clinical and biochemical history showed persistently low total cholesterol (mean 58mg/dl), hypotriglyceridemia, and low LDL-C (mean 13.4mg/dl) over the prior 7 yrs in addition to undetectable serum lipoprotein A. Evaluation for secondary causes of hypolipidemia, such as multiple myeloma, was unremarkable. He was found to have low carotene, borderline vitamin A and low vitamin E levels while the rest of his serum fat-soluble vitamins were normal. His mother who had presumed Alzheimer’s dementia also had a history of very low cholesterol levels. The degree and persistence of his hypolipidemia and hypocholesterolemia raised the possibility of a genetic etiology of his hypolipidemia. Genetic testing confirmed that the patient was heterozygous for a pathogenic variant in the APOB gene, consistent with familial hypobetalipoproteinemia (FHBL) which is autosomal recessive linked. Subsequent close review of his clinical history revealed other potential complications and comorbidities of FHBL including NAFLD with prediabetes, hypogonadism, progressive cognitive and memory decline, peripheral neuropathy and multiple neuropsychiatric syndromes including adult ADHD, borderline personality disorder, bipolar disorder and chronic anxiety. He is presently on vitamin E and A supplementation and being followed by neurology and psychiatry in addition to ongoing endocrine and metabolic clinical surveillance. In addition, in view of his maternal history and several biologic children he has undergone formal genetic and family counselling. Conclusions: While lipid panels are ubiquitous in clinical care, clinicians need to be vigilant in settings of severe persistent hypolipidemia and/or hypocholesterolemia to evaluate for possible genetic basis for this and to also screen for possible associated complications and comorbidities.