27 April 2023: Articles
Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care
Unusual setting of medical care, Rare disease
Aisyah Kamal B , Johanes Dedi Kanchau B , Nur Syahirah Shahuri B , Mohamed-Syarif Mohamed-Yassin D , Noorhida Baharudin D , Suraya Abdul Razak D , Siti Fatimah Badlishah-Sham D , Hasidah Abdul-Hamid D , Aznida Firzah Abdul Aziz D , Alyaa Al-Khateeb D , Yung An Chua D , Noor Alicezah Mohd Kasim D , Siti Hamimah Sheikh Abdul Kadir D , Hapizah Nawawi D , Nadeem Qureshi D , Anis Safura Ramli A*DOI: 10.12659/AJCR.939489
Am J Case Rep 2023; 24:e939489
Table 1. Summary of the genetic mutations of patients presented in this case series.
| Details | Case 1 | Case 2 | Case 3 | |
|---|---|---|---|---|
| Age (years) | 39 | 57 | 41 | |
| Sex | Female | Female | Male | |
| Premature coronary artery disease | No | No | No | |
| ROSE Angina Questionnaire results | Negative | Positive | Negative | |
| Premature cerebrovascular disease | No | No | No | |
| Edinburgh Claudication Questionnaire results | Negative | Negative | Negative | |
| Chronic kidney disease | No | No | No | |
| Diabetes | No | No | No | |
| Hypothyroidism | No | No | No | |
| Premature coronary heart disease (male | YesFather had MI at 46 years of age and CABG at 47 years old | No | No | |
| Premature cerebrovascular or peripheral vascular disease (male | NoMaternal grandfather had a minor stroke at 82 years of age | YesMother had a stroke at 54 years old, deceased from a recurring stroke at 56 years of age | YesMother had a stroke at 60 years old | |
| Hypercholesterolemia | YesFather – on PCSK9 inhibitor; paternal grandfather; paternal uncle; maternal grandfather | YesFather and siblings | No | |
| First degree relatives with corneal arcus | No | YesElder sister & younger brother in their 40s | No | |
| First degree relatives with tendon xanthomas | YesFather, paternal uncle, paternal grandfather | No | No | |
| Xanthomas | YesKnuckles, Achilles tendon, knees | No | No | |
| Premature corneal arcus ( | No | YesPatient noticed since her 30 s | No | |
| Current medication | Atorvastatin 20 mg | Simvastatin 20 mg | Simvastatin 10 mg | |
| The highest TC ever recorded | 10.4 | 8.5 | 7.3 | |
| The highest LDL-c ever recorded | 8.6 | 5.7 | 5.4 | |
| Triglycerides | 1.2 | 0.9 | 2.1 | |
| HDL-c | 1.3 | 2.4 | 0.9 | |
| Simon Broome criteria | Definite | Possible | Possible | |
| DLCC score | 16 | 14 | 4 | |
| FAMCAT relative risk score | 32.3 | 4.4 | 0.6 | |
| Gene | ||||
| Exon | 4 | 26 | 2 | |
| Nucleotide change | c.660del | c.10579C>T | c.277C>T | |
| Chromosome position | chr19-11216238-GC-G | chr2-21229161-G-A | chr1-55509585-C-T | |
| rs number | rs875989905 | rs144467873 | rs151193009 | |
| Amino acid change | p.Asp221fs | p.Arg3527Trp | p.Arg93Cys | |
| Type of mutation | Frameshift (deletion) | Missense | Missense | |
| Pathogenicity of variants based on ACMG Guidelines | Pathogenic | Pathogenic | Likely benign | |
| CKD – chronic kidney disease; TC – total cholesterol; LDL-c – low-density lipo-protein cholesterol; HDL-c – high-density lipoprotein cholesterol; DLCC – Dutch Lipid Clinic Criteria; FAMCAT – familial hypercholesterolemia case ascertainment identification tool; ACMG – American College of Medical Genetics and Genomics. | ||||