Home Medicine The clinical presentation and genetic diagnosis of Tangier disease in the pediatric age group
Article
Licensed
Unlicensed Requires Authentication

The clinical presentation and genetic diagnosis of Tangier disease in the pediatric age group

  • Selcan Öztürk ORCID logo , Muhammet Ensar Doğan , Banu Kadıoğlu Yılmaz ORCID logo , Ayten Güleç , Pembe Soylu Üstkoyuncu , Fatih Kardaş , Hakan Gümüş and Hüseyin Per ORCID logo EMAIL logo
Published/Copyright: January 16, 2025
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 3

Abstract

Objectives

Tangier disease (TD) is a rare autosomal recessive condition characterized by high-density lipoprotein (HDL) deficiency; involving symptoms of polyneuropathy, hyperplastic orange-yellow tonsils, vision disorder, and sudden cardiac death. The major clinical symptoms of TD may not all be co-present. This study evaluates patients diagnosed with TD in childhood to improve the possibility of early diagnosis of asymptomatic cases by reporting our patients’ clinical characteristics in order to minimize delayed diagnosis and emphasize the importance of TD, easily detected by HDL measurement.

Methods

This retrospective and cross-sectional study investigated seven patients from three different families diagnosed with TD.

Results

Four of seven patients were girls. Median age was 5.7 years at symptom onset and 6.5 years at diagnosis. The index case presented with neuropathy findings, and TD was diagnosed based on genetic analysis. Low lipid levels were determined in a sibling and cousins with cardiac death and gait disturbance in the family. TD was confirmed by genetic investigation. Our other patients were evaluated due to anemia, thrombocytopenia, yellow-orange hypertrophy in the tonsils, and organomegaly. Diagnosis was established with genetic analysis and low HDL. No coronary artery disease or ocular involvement was observed in any case.

Conclusions

All patients presenting with neuropathy and gait disorders should undergo detailed tonsil examinations and HDL tests. Genetic analysis should be carried out if necessary. Family screening should be recommended to patients with consanguineous marriages after diagnosis of TD.

Keywords: ABCA1 gene; consanguineous marriage; high-density lipoprotein; orange-yellow tonsils; peripheral neuropathy; tangier disease
Corresponding author: Hüseyin Per, MD, Professor of Pediatric Neurology, Division of Pediatric Neurology, Department of Pediatrics and Child Health, Erciyes University, Faculty of Medicine, 38039, Melikgazi,, Kayseri, Türkiye, E-mail:

Acknowledgments

We thank all the patients and their relatives for their contributions to this research.

  1. Research ethics: This prospective study was approved by the Ethical Committee of the Erciyes University Medical Faculty (Ethic Committee Number: 2021/19).

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: Selcan Öztürk: methodology, conceptualization, writing. Muhammet Ensnare Doğan and Banu Kadıoğlu Yılmaz: writing – reviewing, editing. Ayten Güleç and Pemba Soylu Üstkoyuncu: investigation, writing. Fatih Kardaş and Hakan Gümüş: writing – reviewing, editing. Hüseyin Per: project administration, methodology, supervision.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: The authors did not receive any financial support for the research, authorship, and/or publication of this article.

  7. Data availability: Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request.

References

1. Koseki, M, Yamashita, S, Ogura, M, Ishigaki, Y, Ono, K, Tsukamoto, K, et al.. Current diagnosis and management of Tangier disease. J Atherosclerosis Thromb 2021;28:802–10. https://doi.org/10.5551/jat.RV17053.Search in Google Scholar PubMed PubMed Central

2. Zyss, J, Béhin, A, Couvert, P, Bouhour, F, Sassolas, A, Kolev, I, et al.. Clinical and electrophysiological characteristics of neuropathy associated with Tangier disease. J Neurol 2012;259:1222–6. https://doi.org/10.1007/s00415-011-6340-2.Search in Google Scholar PubMed

3. Jacobo-Albavera, L, Domínguez-Pérez, M, Medina-Leyte, DJ, González-Garrido, A, Villarreal-Molina, T. The role of the ATP-binding cassette A1 (ABCA1) in human disease. Int J Mol Sci 2021;22:1593. https://doi.org/10.3390/ijms22041593.Search in Google Scholar PubMed PubMed Central

4. Karabudak, S, Güzel, V, Güler, B, Uyanık, B, Gürsoy, AE. A case report of Tangier disease presents with acute sensorimotor polyneuropathy and its treatment approach. J Clin Lipidol 2024;18:e285–e289, https://doi.org/10.1016/j.jacl.2023.11.015.Search in Google Scholar PubMed

5. Fitzgerald, ML, Mujawar, Z, Tamehiro, N. ABC transporters, atherosclerosis and inflammation. Atherosclerosis. 2010;211:361–70. https://doi.org/10.1016/j.atherosclerosis.2010.01.011.Search in Google Scholar PubMed PubMed Central

6. Hooper, AJ, Hegele, RA, Burnett, JR. Tangier disease: update for 2020. Curr Opin Lipidol 2020;31:80–4. https://doi.org/10.1097/MOL.0000000000000669.Search in Google Scholar PubMed

7. Fredrickson, DS, Altrocchi, PH, Avioli, LV, Goodman, DS, Goodman, HC. Tangier disease. Ann Intern Med 1961; 55: 1016–31, https://doi.org/10.7326/0003-4819-55-6-1016.Search in Google Scholar

8. Smith, SA. Acquired peripheral neuropathies. In: Swaiman’s pediatric neurology, principles and practice, 6th ed. Amsterdam, Netherlands: Elsevier; 2018:1082–5 pp.10.1016/B978-0-323-37101-8.00142-9Search in Google Scholar

9. Dumitru, RM. Genetic susceptibility in biochemical and physiological traits. In: Cardiovascular diseases, Chapter 9. 1st ed. Elsevier; 2016:177–217 pp.10.1016/B978-0-12-803312-8.00009-4Search in Google Scholar

10. Per, H, Canpolat, M, Ulgen, E, Baran, B, Kardas, F, Gumus, H, et al.. Clinical, electrodiagnostic, and genetic features of Tangier disease in an adolescent girl with presentation of peripheral neuropathy. Neuropediatrics 2015;46:420–3. https://doi.org/10.1055/s-0035-1565275.Search in Google Scholar PubMed

11. Liang, Z, Li, W, Yang, S, Liu, Z, Sun, X, Gao, X, et al.. Tangier disease may cause early onset of atherosclerotic cerebral infarction: a case report. Medicine (Baltim) 2018;97:e12472. https://doi.org/10.1097/MD.0000000000012472.Search in Google Scholar PubMed PubMed Central

12. Burnett, JR, Hooper, AJ, McCormick, SPA, Hegele, RA. Tangier disease. In: Adam, MP, Feldman, J, Mirzaa, GM, Pagon, RA, Wallace, SE, Bean, LJH, et al.., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 2019:1993–2024 pp. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1380/.Search in Google Scholar

13. Schaefer, EJ, Santos, RD, Asztalos, BF. Marked HDL deficiency and premature coronary heart disease. Curr Opin Lipidol 2010;21:289–97. https://doi.org/10.1097/MOL.0b013e32833c1ef6.Search in Google Scholar PubMed PubMed Central

14. Suehiro, T, Ikeda, Y. Tangier disease. Nihon Rinsho Jpn J Clin Med 2007;65:604-7. PMID: 17824095.Search in Google Scholar

15. Mercan, M, Yayla, V, Altinay, S, Seyhan, S. Peripheral neuropathy in Tangier disease: a literature review and assessment. J Peripher Nerv Syst 2018;23:88–98. https://doi.org/10.1111/jns.12265.Search in Google Scholar PubMed

16. Colaco, A, Kaya, E, Adriaenssens, E, Davis, LC, Zampieri, S, Fernández-Suárez, ME, et al.. Mechanistic convergence and shared therapeutic targets in Niemann-Pick disease. J Inherit Metab Dis 2020;43:574–85. https://doi.org/10.1002/jimd.12191.Search in Google Scholar PubMed PubMed Central

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jpem-2024-0335).

Video 1
Received: 2024-07-13
Accepted: 2024-11-21
Published Online: 2025-01-16
Published in Print: 2025-03-26

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Original Articles
  3. Thyroid surgery in pediatric age: a 10-year experience at a single center and literature review
  4. Differentiated thyroid cancer in adolescents – does extent of disease at presentation differ with age?
  5. Evaluation of iodine and selenium level and thyroid functions in patients with cystic fibrosis
  6. Interpreting positive celiac serology in children with new-onset type 1 diabetes
  7. Elastographic evaluation for fatty liver disease in north Indian children and adolescents with type 1 diabetes
  8. Diagnostic value of fasting insulin and insulin-like growth factor-1 levels in girls with central precocious puberty
  9. Clinical outcomes of switching to lonapegsomatropin from somatropin for treatment of pediatric growth hormone deficiency
  10. Development of a disease diagnostic model to predict the occurrence of central precocious puberty of female
  11. Adrenal hypoandrogenism in adolescents with premature ovarian insufficiency
  12. The clinical presentation and genetic diagnosis of Tangier disease in the pediatric age group
  13. Clinical and genetic diagnosis of first cohort of differences of sexual development in the Iranian population
  14. Short Communication
  15. Effect of a GnRH injection on kisspeptin levels in girls with suspected precocious puberty: a randomized-controlled pilot study
  16. Case Reports
  17. Coexistence of phenylketonuria and tyrosinemia type 3: challenges in the dietary management
  18. Acrodermatitis dysmetabolica: lessons from two pediatric cases
  19. Dramatic response to Evinacumab in a North Indian girl with homozygous familial hypercholesterolemia
https://doi.org/10.1515/jpem-2024-0335
Keywords for this article
ABCA1 gene; consanguineous marriage; high-density lipoprotein; orange-yellow tonsils; peripheral neuropathy; tangier disease

Articles in the same Issue

  1. Frontmatter
  2. Original Articles
  3. Thyroid surgery in pediatric age: a 10-year experience at a single center and literature review
  4. Differentiated thyroid cancer in adolescents – does extent of disease at presentation differ with age?
  5. Evaluation of iodine and selenium level and thyroid functions in patients with cystic fibrosis
  6. Interpreting positive celiac serology in children with new-onset type 1 diabetes
  7. Elastographic evaluation for fatty liver disease in north Indian children and adolescents with type 1 diabetes
  8. Diagnostic value of fasting insulin and insulin-like growth factor-1 levels in girls with central precocious puberty
  9. Clinical outcomes of switching to lonapegsomatropin from somatropin for treatment of pediatric growth hormone deficiency
  10. Development of a disease diagnostic model to predict the occurrence of central precocious puberty of female
  11. Adrenal hypoandrogenism in adolescents with premature ovarian insufficiency
  12. The clinical presentation and genetic diagnosis of Tangier disease in the pediatric age group
  13. Clinical and genetic diagnosis of first cohort of differences of sexual development in the Iranian population
  14. Short Communication
  15. Effect of a GnRH injection on kisspeptin levels in girls with suspected precocious puberty: a randomized-controlled pilot study
  16. Case Reports
  17. Coexistence of phenylketonuria and tyrosinemia type 3: challenges in the dietary management
  18. Acrodermatitis dysmetabolica: lessons from two pediatric cases
  19. Dramatic response to Evinacumab in a North Indian girl with homozygous familial hypercholesterolemia
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 19.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2024-0335/html
Scroll to top button