Heterozygous Null LDLR Mutation in a Familial Hypercholesterolemia Patient With an Atypical Presentation Because of Alcohol Abuse
Patients with familial hypercholesterolemia (FH; Online Mendelian Inheritance in Man #143890) have lifelong elevations in low-density lipoprotein cholesterol (LDL-C) that result in deposition of cholesterol in tendons— referred to as tendon xanthomas and occurring in ≈19% of heterozygous FH patients1—and an increased risk of premature cardiovascular disease. FH is an autosomal dominant disorder resulting from mutations in the LDL receptor (LDLR), APOB(apolipoprotein B), or PCSK9(proprotein convertase subtilisin-like kexin type 9) genes.2
Heterozygous mutations in LDLR are the most common cause of FH. In addition to elevated LDL-C, patients harboring LDLR mutations may have lower levels of high-density lipoprotein cholesterol and only mild, if any, elevations in triglycerides.3–5 Severe hypertriglyceridemia is rarely seen in FH patients.5 We report an alcoholic patient who presented with severely elevated serum triglycerides and both tuberous and tendon xanthomas in whom the diagnosis of FH was confirmed by genetic testing.
A 75-year-old Hispanic man was referred to us for genetic testing as part of a larger research protocol.6 His medical history included 3-vessel coronary artery bypass graft at age 47 and a myocardial infarction at age 60, hypothyroidism, osteoporosis, gastro-esophageal reflux, hypertension, recurrent major depressive disorder with a history of a suicide attempt, heavy alcohol and tobacco abuse, and Alzheimer dementia (initially diagnosed at age 72 with superimposed frontal lobe damage from prior alcohol use).
Hyperlipidemia was first diagnosed at age 34, although his wife noted that he had Achilles tendon xanthomas and arcus senilis since age 22 (when they first met). He had been tried on multiple medications (he could not recall exact names) and ultimately underwent ileal bypass surgery at age 41 for treatment. The ileal bypass was reversed at age 60 because of multiple episodes of intestinal obstruction. At age 66, he was …