Xanthomas Can Be Misdiagnosed and Mistreated in Homozygous Familial Hypercholesterolemia Patients: A Call for Increased Awareness Among Dermatologists and Health Care Practitioners

Glob Heart. 2020 Feb 28;15(1):19. doi: 10.5334/gh.759.

Abstract

Background: Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disorder and results in the development of coronary artery disease (CAD). Clinical diagnosis of homozygous HH patients is usually straightforward because persistent hypercholesterolemia can produce xanthoma and corneal arcus. However, xanthoma may also be misdiagnosed as skin lesions and could therefore be mistreated. The aim of this case study report is to highlight the plight of patients with FH as means of raising awareness of the condition among dermatologists and health care practitioners, also to determine the genotype-phenotype correlation in severely affected homozygous FH proband patients.

Methods: Genetic screening of FH associated genes was performed by Ion Torrent next-generation sequencing and cascade screening by capillary sequencing.

Results: We present two clinical cases with prominent skin lesions seen in a dermatology clinic that were referred to plastic surgery for excision. Genetic testing was performed later, and confirmed common single nucleotide deletion variant (c.2027delG) in the LDLR alleles consequent to a frameshift mutation p.(G676Afs*33). In addition to the LDLR variant, two possibly damaging APOB variants p.(L3313I) and p.(L1212M) and three damaging variants p.(R19*), p.(G83Q) and p.(S474*) in APOC3, PON2 and LPL genes respectively were identified. The PON2 gene variant p.(G83Q) was found to be novel, while others have been previously reported. Both patients were refractory to pharmacological therapies and are currently on lipoprotein apheresis (LA).

Conclusions: The present report indicates the need for increased awareness of FH, among the public and healthcare practitioners and supports the need for diagnostic screening and cascade genetic testing of this high-risk condition, which could ultimately lead to better prevention of CHD in this lethal condition.

Keywords: Cholesterol; Coronary artery disease; Familial hypercholesterolemia; Frameshift mutation; Low-density lipoprotein receptor; Mutation; Next-generation sequencing; Xanthoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Awareness*
  • Child
  • Clinical Competence*
  • Dermatologists / psychology*
  • Diagnostic Errors
  • Female
  • Genetic Testing / methods*
  • Genetic Variation
  • Health Personnel / psychology*
  • Humans
  • Hyperlipoproteinemia Type II / diagnosis*
  • Hyperlipoproteinemia Type II / genetics
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Xanthomatosis / diagnosis*
  • Xanthomatosis / genetics
  • Young Adult

Grants and funding

It is our great pleasure to sincerely acknowledge the contribution of the probands and their family members who cooperated in this investigation. The authors would also like to thank the Science and Technology Unit at Umm Al-Qura University for its continuous support. Editorial assistance was provided by Nigel Eastmond of Eastmond Medicomm Ltd, which was funded by the Prince Sultan Cardiac Centre. The study was supported by a grant (number: 08-BIO34-10), from National Science, Technology and Innovation Plan (MAARIFAH), Kingdom of Saudi Arabia.