Turk Kardiyol Dern Ars. Ahead of Print: TKDA-62185 | DOI: 10.5543/tkda.2020.62185
Monozygotic twins with familial hypercholesterolemia and high Lipoprotein(a) levels leading to identical cardiovascular outcomes: case report and review of the literature
, Hakan Gokalp Uzun1
, aslı tetik vardarlı2
, Lale Tokgozoglu31
Ege University Medical Faculty, Department of Cardiology, Izmir, Turkey, 2
Ege University Medical Faculty, Department of Medical Biology, Izmir, Turkey, 3
Hacettepe University Medical Faculty, Department of Cardiology, Ankara, Turkey.
Homozygous familial hypercholesterolaemia (HoFH) is a rare, autosomal dominant disease leading to premature cardiovascular (CV) disease. As monozygotic twins share intrauterine environment, age and all their genes, they could represent a very special resource for investigating the causes and natural course of FH. Herein, we report 36-year-old monozygotic twin brothers with almost identical early coronary artery involvement due to FH concomitant with high lipoprotein a (Lpa) levels with literature review. Keywords:
Sequence analysis revealed that twins were homozygote for LDLR c.1060+10G>A (rs12710260) mutation and heterozygote for LDLR c.542C>T (rs557344672) mutations. Both were also homozygote for c.1060+7T>C (rs2738442), c.1586+53A>G (rs1569372) mutations in LDLR gene and c.4265A>T (rs568413) mutations in APOB gene.
In the literature there are 7 twin cases reported for FH, and none for high Lpa levels. Our HoFH twins had lower LDL levels than expected (before treatment 204 and 223 mg/dL), with almost identical coronary involvement. Both had extremely high Lpa levels (308 and 272 nmol/L) with very low coronary calcium score (16 AU) and good response to statins (> 60%). Moreover, the first CV events were almost occurring at the same ages (i.e. 32-34 years of age) in the family. This could be an important aspect of FH families due to similar timing of cumulative LDL exposure exceeding the threshold of CV events.
In conclusion, the first report of monozygotic HoFH twins with elevated Lpa levels and almost identical early coronary artery involvement at the same ages provides an evidence to substantiate the hypothesis of life-time cholesterol burden/exposure.
familial hypercholesterolemia, LDL-cholesterol, lipoprotein (a), premature cardiovascular disease
How to cite this article
Corresponding Author: Meral Kayikcioglu, Türkiye