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Abstract

Congenital atransferrinemia is an extremely rare autosomal recessive disorder characterized by functional or quantitative deficiency of transferrin. This leads to a characteristic clinical picture that includes heart failure due to iron overload cardiomyopathy, severe anemia, as well as hepatic and endocrine dysfunction in early infancy. Although rare or may be underdiagnosed, congenital atransferrinemia is a treatable cause of infantile heart failure and iron overload cardiomyopathy. Therefore, it is important to keep this diagnosis as a possibility in childhood presentation of heart failure and anemia. Early diagnosis and timely treatment can prevent progressive myocardial dysfunction and recurrent heart failure. This article focuses on pathophysiology, diagnosis, genetics, and management of heart failure in congenital atransferrinemia.

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2025-11-10
2025-12-24

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References

  1. Dabboubi R. A new case of congenital atransferrinemia with a novel splice site mutation: c.293-63del. European. J. Med. Genetic 2020 63 5 103874 10.1016/j.ejmg.2020.103874
    [Google Scholar]
  2. Heilmeyer L. Keller W. Vivell O. Betke K. Woehler F. Keiderling W.Congenital atransferrinemia] Schweiz. Med. Wochenschr. 1961 91 1203 [Congenital atransferrinemia 13906009
    [Google Scholar]
  3. Knisely A.S. Gelbart T. Beutler E. Molecular characterization of a third case of human atransferrinemia. Blood 2004 104 8 2607 10.1182/blood‑2004‑05‑1751 15466165
    [Google Scholar]
  4. Aslan D. Crain K. Beutler E. A new case of human atransferrinemia with a previously undescribed mutation in the transferrin gene. Acta Haematol. 2007 118 4 244 247 10.1159/000112726 18097132
    [Google Scholar]
  5. Hayashi A. Wada Y. Suzuki T. Shimizu A. Studies on familial hypotransferrinemia: unique clinical course and molecular pathology. Am. J. Hum. Genet. 1993 53 1 201 213 8317485
    [Google Scholar]
  6. Dimitrios T. Kremastinos, dimitrios farmakis. iron overload cardiomyopathy in clinical practice. CirculationVolume 2011 124 20 2253 2263 10.1161/CIRCULATIONAHA.111.050773
    [Google Scholar]
  7. Gomme P.T. Transferrin: Structure, function and Potential therapeutic actions. Discov Today 2005 10 267 273 10.1016/S1359‑6446(04)03333‑1
    [Google Scholar]
  8. Siah Christopher W Ombiga John. Adams Leon A. Trinder Debbie Olynyk John K. Normal iron metabolism and the pathophysiology of iron overload disorders. Clin. Biochem. Rev. 2006 27 S5 S11 1692558
    [Google Scholar]
  9. Dunn L.L. Rahmanto Y.S. Richardson D.R. Iron uptake and metabolism in the new millennium. Trends Cell Biol. 2007 17 2 93 100 10.1016/j.tcb.2006.12.003 17194590
    [Google Scholar]
  10. Pietrangelo A. Torbenson M. Disorders of Iron Overload. In:MacSween’s Pathology of the Liver. Elsevier Inc. 2017 275 307 10.1016/B978‑0‑7020‑6697‑9.00004‑2
    [Google Scholar]
  11. Pietrangelo A. Hereditary hemochromatosis: A new look at an old disease. N. Engl. J. Med. 2004 350 23 2383 2397 10.1056/NEJMra031573 15175440
    [Google Scholar]
  12. Gujja P. Rosing D.R. Tripodi D.J. Shizukuda Y. Iron overload cardiomyopathy: Better understanding of an increasing disorder. J. Am. Coll. Cardiol. 2010 56 13 1001 1012 10.1016/j.jacc.2010.03.083 20846597
    [Google Scholar]
  13. Rivella Stefano Crielaard, Bart Disorders of iron metabolism: Iron deficiency and iron overload and anemia of chronic diseases. In:Pathobiology of Human Disease. Elsevier 2014 1471 1487 10.1016/B978‑0‑12‑386456‑7.07903‑X
    [Google Scholar]
  14. Lubitz S.A. Goldbarg S.H. Mehta D. Sudden cardiac death in infiltrative cardiomyopathies: sarcoidosis, scleroderma, amyloidosis, hemachromatosis. Prog. Cardiovasc. Dis. 2008 51 1 58 73 10.1016/j.pcad.2007.10.003 18634918
    [Google Scholar]
  15. Nielsen P. Engelhardt R. Düllmann J. Fischer R. Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritin iron as new diagnostic parameters in hereditary hemochromatosis. Blood Cells Mol. Dis. 2002 29 3 451 458 10.1006/bcmd.2002.0583 12547235
    [Google Scholar]
  16. Anderson L.J. Assessment of iron overload with T2* magnetic resonance imaging. Prog. Cardiovasc. Dis. 2011 54 3 287 294 10.1016/j.pcad.2011.07.004 22014495
    [Google Scholar]
  17. He T. Cardiovascular magnetic resonance T2* for tissue iron assessment in the heart. Quant. Imaging Med. Surg. 2014 4 5 407 412 25392825
    [Google Scholar]
  18. Wood J.C. History and current impact of cardiac magnetic resonance imaging on the management of iron overload. Circulation 2009 120 20 1937 1939 10.1161/CIRCULATIONAHA.109.907196 19884464
    [Google Scholar]
  19. Shehata S.M. Amin M.I. Zidan E.S.H. MRI evaluation of hepatic and cardiac iron burden in pediatric thalassemia major patients: Spectrum of findings by T2*. Egypt. J. Radiol. Nucl. Med. 2019 50 1 68 10.1186/s43055‑019‑0044‑5
    [Google Scholar]
  20. Wood J.C. Cardiac iron across different transfusion-dependent diseases. Blood Rev. 2008 22 Suppl. 2 S14 S21 10.1016/S0268‑960X(08)70004‑3 19059052
    [Google Scholar]
  21. Garbowski M.W. Carpenter J.P. Smith G. Roughton M. Alam M.H. He T. Pennell D.J. Porter J.B. Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 Ferriscan. J. Cardiovasc. Magn. Reson. 2014 16 1 40 10.1186/1532‑429X‑16‑40 24915987
    [Google Scholar]
  22. Beutler E. Gelbart T. Lee P. Trevino R. Fernandez M.A. Fairbanks V.F. Molecular characterization of a case of atransferrinemia. Blood 2000 96 13 4071 4074 10.1182/blood.V96.13.4071 11110675
    [Google Scholar]
  23. Nazir H. Al-Khabori M.K. Kohistani N. Puchalka J. Klein C. A rare case of congenital atransferrinemia: international collaboration for genetic diagnosis. Blood 2014 124 21 4883 10.1182/blood.V124.21.4883.4883
    [Google Scholar]
  24. Athiyarath R. Two novel missense mutations in iron transport protein transferrin causing microcytic hypochromic anemia and hemosiderosis, molecular characterization and structural implications. BrJHematolol 2013 163 103 104
    [Google Scholar]
  25. Murphy C.J. Oudit G.Y. Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment. J. Card. Fail. 2010 16 11 888 900 10.1016/j.cardfail.2010.05.009 21055653
    [Google Scholar]
  26. McMurray J.J.V. Packer M. Desai A.S. Gong J. Lefkowitz M.P. Rizkala A.R. Rouleau J.L. Shi V.C. Solomon S.D. Swedberg K. Zile M.R. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N. Engl. J. Med. 2014 371 11 993 1004 10.1056/NEJMoa1409077 25176015
    [Google Scholar]
  27. McMurray J.J.V. Solomon S.D. Inzucchi S.E. Køber L. Kosiborod M.N. Martinez F.A. Ponikowski P. Sabatine M.S. Anand I.S. Bělohlávek J. Böhm M. Chiang C.E. Chopra V.K. de Boer R.A. Desai A.S. Diez M. Drozdz J. Dukát A. Ge J. Howlett J.G. Katova T. Kitakaze M. Ljungman C.E.A. Merkely B. Nicolau J.C. O’Meara E. Petrie M.C. Vinh P.N. Schou M. Tereshchenko S. Verma S. Held C. DeMets D.L. Docherty K.F. Jhund P.S. Bengtsson O. Sjöstrand M. Langkilde A.M. Dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF). N. Engl. J. Med. 2019 381 21 1995 2008 10.1056/NEJMoa1911303 31535829
    [Google Scholar]
  28. Shaddy R. Design for the sacubitril/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study). American Heart J. 2017 193 23 34 10.1016/j.ahj.2017.07.006
    [Google Scholar]
  29. Corradini E. Buzzetti E. Pietrangelo A. Genetic iron overload disorders. Mol. Aspects Med. 2020 75 100896 10.1016/j.mam.2020.100896 32891497
    [Google Scholar]
  30. Caines A.E. Kpodonu J. Massad M.G. Chaer R. Evans A. Lee J.C. Geha A.S. Cardiac transplantation in patients with iron overload cardiomyopathy. J. Heart Lung Transplant. 2005 24 4 486 488 10.1016/j.healun.2004.02.009 15797753
    [Google Scholar]
/content/journals/chddt/10.2174/011871529X399774251016072809
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Revisiting Congenital Atransferrinemia: A Rare but Treatable Cause of Pediatric Heart Failure
Bentham Science Publishers ; https://doi.org/10.2174/011871529X399774251016072809
/content/journals/chddt/10.2174/011871529X399774251016072809
/content/journals/chddt/10.2174/011871529X399774251016072809
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  • Article Type:     Review Article
Keywords: anemia ; Pediatric heart failure ; atransferrinemia ; myocardial ; iron overload cardiomyopathy

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