A Japanese Case of Familial Hypercholesterolemia with a Protein-truncating Variant in LDLR and a PCSK9 Variant without Significant Atherosclerosis but Showing Remarkable Achilles Tendon Thickening

Intern Med. 2024;63(15):2137-2142. doi: 10.2169/internalmedicine.2726-23. Epub 2024 Aug 1.

Abstract

The patient was a 54-year-old woman with familial hypercholesterolemia and remarkable Achilles tendon thickening. At 20 years old, the patient had a total cholesterol level of approximately 300 mg/dL. She started receiving rosuvastatin (5 mg/day) for low-density lipoprotein cholesterol (LDL-C) 235 mg/dL at 42 years old, which was increased to 10 mg/day at 54 years old, decreasing her serum LDL-C level to approximately 90 mg/dL. The serum Lp (a) level was 9 mg/dL. A computed tomography coronary angiogram showed no significant stenosis. Next-generation sequencing revealed a frameshift variant in LDL receptor (LDLR) (heterozygous) and a missense variant in proprotein convertase subtilisin/kaxin type 9 (PCSK9) (heterozygous). Continued statin therapy, in addition to low Lp (a) and female sex, can help prevent cardiovascular disease.

Keywords: Lp (a); PCSK9 variant; a protein-truncating variant in the LDLR; computerized tomography (CT) coronary angiogram; heterozygous familial hypercholesterolemia.

Publication types

  • Case Reports

MeSH terms

  • Achilles Tendon* / diagnostic imaging
  • Achilles Tendon* / pathology
  • Atherosclerosis / genetics
  • Cholesterol, LDL / blood
  • East Asian People
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipoproteinemia Type II* / blood
  • Hyperlipoproteinemia Type II* / complications
  • Hyperlipoproteinemia Type II* / diagnosis
  • Hyperlipoproteinemia Type II* / drug therapy
  • Hyperlipoproteinemia Type II* / genetics
  • Japan
  • Middle Aged
  • Mutation, Missense
  • Proprotein Convertase 9* / genetics
  • Receptors, LDL* / genetics
  • Rosuvastatin Calcium / therapeutic use

Substances

  • Receptors, LDL
  • Proprotein Convertase 9
  • PCSK9 protein, human
  • LDLR protein, human
  • Rosuvastatin Calcium
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol, LDL