Xanthomas Can Be Misdiagnosed and Mistreated in Homozygous Familial Hypercholesterolemia Patients: A Call for Increased Awareness Among Dermatologists and Health Care Practitioners
Fahad Alnouri,
Faisal A. Al-Allaf,
Mohammad Athar,
Zainularifeen Abduljaleel,
Moheeb Alabdullah,
Dalal Alammari,
Menwar Alanazi,
Fahmi Alkaf,
Abeer Allehyani,
Mohammad A. Alotaiby,
Abdullah Alshehri,
Abdellatif Bouazzaoui,
Hussam Karrar,
Mohiuddin M. Taher
Affiliations
Fahad Alnouri
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh
Faisal A. Al-Allaf
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah Al Mukarramah; Science and Technology Unit, Umm Al-Qura University, Makkah Al Mukarramah; Molecular Diagnostics Unit, Department of Laboratory and Blood Bank, King Abdullah Medical City, Makkah Al Mukarramah
Mohammad Athar
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah Al Mukarramah; Science and Technology Unit, Umm Al-Qura University, Makkah Al Mukarramah
Zainularifeen Abduljaleel
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah Al Mukarramah; Science and Technology Unit, Umm Al-Qura University, Makkah Al Mukarramah
Moheeb Alabdullah
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh
Dalal Alammari
Department of Dermatology, Prince Sultan Military Medical City, Riyadh
Menwar Alanazi
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh
Fahmi Alkaf
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh
Abeer Allehyani
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh
Mohammad A. Alotaiby
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh
Abdullah Alshehri
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh
Abdellatif Bouazzaoui
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah Al Mukarramah; Science and Technology Unit, Umm Al-Qura University, Makkah Al Mukarramah
Hussam Karrar
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh
Mohiuddin M. Taher
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah Al Mukarramah; Science and Technology Unit, Umm Al-Qura University, Makkah Al Mukarramah
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.
