Combination of familial transthyretin amyloidosis and hyperlipoproteinemia(a) in a patient with spinal canal stenosis: a case report

Cover Image

Cite item

Full Text

Abstract

Hereditary transthyretin amyloidosis is a rare, progressive, systemic autosomal dominant disorder characterized by the extracellular deposition of insoluble amyloid fibrils in the peripheral nervous system, heart, and other organs. Among the specific signs of this condition, symptomatic spinal canal stenosis is prominent. Lipoprotein(a) is an atherogenic lipoprotein, and increased plasma concentrations are a significant risk factor for cardiovascular and cerebrovascular diseases. Data regarding the relationship between transthyretin amyloidosis and lipoprotein(a) levels are limited.

This article presents a clinical case of a patient with arterial hypertension, with blood pressure elevated to 150/90 mmHg for 5 years. Following a COVID-19 infection between June 2, 2021, and June 25, 2021, the patient experienced a marked increase in blood pressure to 290/150 mmHg; sharp left-sided chest pain lasting 20–30 minutes unrelated to physical activity, which was relieved with medication; and pain in the cervical and thoracic spine. Despite antihypertensive therapy, the patient’s blood pressure stabilized at 110/70 mmHg. Further evaluation revealed dyslipidemia, with increased low-density lipoprotein cholesterol levels at 4.53 mmol/L and lipoprotein(a) at 1.46 g/L. Doppler ultrasound revealed atherosclerosis in the extracranial parts of the brachiocephalic arteries, with up to 20% stenosis of the right internal carotid artery. Echocardiography showed thickening of the left ventricular wall, interatrial septum, and mitral valve leaflets, although the ejection fraction remained preserved. Magnetic resonance imaging of the spine revealed cervical spinal canal stenosis (C5–C6). Genetic testing identified a nucleotide sequence variant in the transthyretin gene (Chr18: 29171879 G>A, p. Arg5His) in the heterozygous state in the patient and her blood relatives. Specific anti-amyloid therapy with tafamidis was considered, and hypolipidemic therapy was initiated.

In patients with symptomatic spinal canal stenosis and left ventricular wall thickening, even in the presence of hypertension, comprehensive evaluation is crucial for the timely diagnosis and adequate management of amyloid cardiomyopathy. Thus, we describe the first reported clinical case of the combination of familial transthyretin amyloidosis and hyperlipoproteinemia(a).

About the authors

Thanh L. Nguyen

108 Military Central Hospital

Author for correspondence.
Email: truongthianh0302@gmail.com
ORCID iD: 0000-0002-8856-4542
SPIN-code: 9408-1899

MD, Cand. Sci. (Medicine)

Viet Nam, Hanoi

Elena V. Reznik

City Clinical Hospital No 31 named after academician G.M. Savelieva; The Russian National Research Medical University named after N.I. Pirogov

Email: elenaresnik@gmail.com
ORCID iD: 0000-0001-7479-418X
SPIN-code: 3494-9080

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow; Moscow

References

  1. Reznik EV, Nguyen TL, Dikaeva MS, et al. Features of diagnostics and course of hypertrophic cardiomyopathy in real clinical practice. The Russian Archives of Internal Medicine. 2023;13(3):181–195. doi: 10.20514/2226-6704-2023-13-3-181-195 EDN: GGLHPG
  2. Reznik EV, Stepanova EA, Nguyen TL, et al. Retrospective analysis of cardiovascular involvement in patients with systemic amyloidosis. Cardiovascular Therapy and Prevention. 2021;20(1):35–46. doi: 10.15829/1728-8800-2021-2496 EDN: BYPVBU
  3. Reznik EV, Nguyen TL, Kudryavtseva MM, et al. Comparison of cardiac amyloidosis and hypertrophic cardiomyopathy: retrospective analysis of cardiac and kidney lesion. Russian Journal of Cardiology. 2023;28(11):5444. doi: 10.15829/15604071-2023-5444 EDN: JKLPYR
  4. Miksenas H, Januzzi JL, Natarajan P. Lipoprotein(a) and cardiovascular diseases. JAMA. 2021;326(4):352–353. doi: 10.1001/jama.2021.3632 EDN: OEOYNY
  5. Westermark P. The pathogenesis of amyloidosis: understanding general principles. Am J Pathol. 1998;152(5):1125–1127.
  6. Nikitin SS, Bardakov SN, Suponeva NA, et al. Phenotypic heterogeneity and diagnostic features of transthyretin amyloidosis with polyneuropathy. Neuromuscular Diseases. 2021;11(3):12–36. doi: 10.17650/2222-8721-2021-11-3-12-36 EDN: MSVKOX
  7. Rameev VV, Myasnikov RP, Vinogradov PP, et al. Systemic ATTR-amyloidosis, a rare form of internal organ damage. Rational Pharmacotherapy in Cardiology. 2019;15(3):349–358 doi: 10.20996/1819-6446-2019-15-3-349-358 EDN: VNIHZD
  8. Moore ZJ, Rizkalla JM, Weiner J, et al. Transthyretin amyloidosis in spinal canal stenosis: a systematic review. J Orthop. 2024;53:133–139. doi: 10.1016/j.jor.2024.02.047 EDN: NTUUWN
  9. Reznik EV, Nguyen TL, Ustyuzhanin DV, et al. Red flags to diagnose infiltrative cardiomyopathies. Russian Journal of Cardiology. 2023;28(1S):40–51. doi: 10.15829/1560-4071-2023-5259 EDN: ZGFWNJ
  10. Reznik EV, Nguyen TL, Stepanova EA, et al. Cardiac amyloidosis: internist and cardiologist insight. The Russian Archives of Internal Medicine. 2020;10(6):430–457. doi: 10.20514/2226-6704-2020-10-6-430-457 EDN: VHNDGN
  11. Dungu JN, Valencia O, Pinney JH, et al. CMR-based differentiation of AL and ATTR cardiac amyloidosis. JACC: Cardiovascular Imaging. 2014;7(2):133–142. doi: 10.1016/j.jcmg.2013.08.015
  12. Vergaro G, Aimo A, Barison A, et al. Keys to early diagnosis of cardiac amyloidosis: red flags from clinical, laboratory and imaging findings. European Journal of Preventive Cardiology. 2020;27(17):1806–1815. doi: 10.1177/2047487319877708 EDN: ACLJFW
  13. Vogel J, Carpinteiro A, Luedike P, et al. Current therapies and future horizons in cardiac amyloidosis treatment. Curr Heart Fail Rep. 2024;21(4):305–321. doi: 10.1007/s11897-024-00669-7 EDN: HFSLBF
  14. McDonagh TA, Gardner RS, Baumbach A, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the heart failure association (HFA) of the ESC. European Journal of Heart Failure. 2022;24(1):4–131. doi: 10.1002/ejhf.2333 EDN: VGUJJF
  15. Chan DC, Watts GF. The promise of PCSK9 and lipoprotein(a) as targets for gene silencing therapies. Clinical Therapeutics. 2023;45(11):1034–1046. doi: 10.1016/j.clinthera.2023.07.008 EDN: QRJECJ
  16. Madsen CM, Kamstrup PR, Langsted A, et al. Lipoprotein(a)-lowering by 50 mg/dL (105 nmol/L) may be needed to reduce cardiovascular disease 20% in secondary prevention. Arteriosclerosis, Thrombosis, and Vascular Biology. 2020;40(1):255–266. doi: 10.1161/ATVBAHA.119.312951
  17. Handelmann G, Boyles J, Weisgraber K, et al. Effects of apolipoprotein E, beta-very low density lipoproteins, and cholesterol on the extension of neurites by rabbit dorsal root ganglion neurons in vitro. Journal of Lipid Research. 1992;33:1677–1688. doi: 10.1016/S0022-2275(20)41390-2
  18. Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis: An Official Journal of the American Heart Association. 1988;8(1):1–21. doi: 10.1161/01.ATV.8.1.1
  19. Genschel J, Haas R, Pröpsting MJ, et al. Apolipoprotein A-I induced amyloidosis. FEBS Letters. 1998;430(3):145–149. doi: 10.1016/S0014-5793(98)00668-1 EDN: PLCHLI
  20. Tanaka Y, Ando Y, Kumamoto T, et al. Changed affinity of apolipoprotein AII to high density lipoprotein (HDL) in patients with familial amyloidotic polyneuropathy (FAP) type I. Biochimica et Biophysica Acta (BBA) — Molecular Basis of Disease. 1994;1225(3):311–316. doi: 10.1016/0925-4439(94)90012-4
  21. Sousa MM, Berglund L, Saraiva MJ. Transthyretin in high density lipoproteins: association with apolipoprotein A-I. Journal of Lipid Research. 2000;41(1):58–65. doi: 10.1016/S0022-2275(20)32074-5
  22. Ryabova AY, Guzenko TN, Bykova AP, et al. Arterial hypertension and Covid-19: possible relationships. Modern Problems of Science and Education. 2023;(2):102. doi: 10.17513/spno.32438 EDN: VCQHPR

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Twelve-lead electrocardiogram of a patient with familial transthyretin amyloidosis and hyperlipoproteinemia(a).

Download (545KB)
Indexing metadata
3. Fig. 2. Echocardiography findings in the patient: a, thickening of the interventricular and interatrial septa (white arrows); b, thickening of the anterior mitral valve leaflet (white arrow).

Download (137KB)
Indexing metadata
4. Fig. 3. Pedigree of the patient with familial transthyretin amyloidosis. Circles represent females; squares represent males. The family members with a confirmed mutation are marked in black, those without the mutation in white, and those not yet tested (testing planned) in gray. The year of birth is indicated in figures. AF, atrial fibrillation (in the patient’s father); Lp(a), increased lipoprotein(a) levels in the patient and her father (not assessed in other family members because of technical reasons).

Download (80KB)
Indexing metadata
5. Fig. 5. Twelve-lead electrocardiogram of the patient’s father: a, standard and augmented limb leads recorded at 25 mm/s; b, precordial leads recorded at 50 mm/s. Standard calibration: 1 mV corresponds to a 10-mm deflection.

Download (286KB)
Indexing metadata
6. Fig. 4. Timeline of disease progression in the patient with familial transthyretin amyloidosis and hyperlipoproteinemia(a). PCR, polymerase chain reaction; LDL, low-density lipoprotein; Lp(a), lipoprotein(a); MRI, magnetic resonance imaging; EchoCG, echocardiography; ENMG, electroneuromyography; RPH, radiopharmaceutical; SSR, sympathetic skin response; C, cervical spine; pelacarsen is not authorized in the Russian Federation.

Download (415KB)
Indexing metadata

Copyright (c) 2025 Eco-Vector

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).