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Rare Anemias

Muckenthaler/Kunz/Kulozik Research Group

I.  Research areas

Congenital blood disorders include a wide range of very rare diseases.
The disorders may impair the functioning or formation of hemoglobin, of the coagulation factors in the plasma or of the blood cells themselves. Each of these diseases affects less than 1000 people in Germany.
At Heidelberg University Hospital, we look back on many years of experience in treating all forms of congenital blood disorders:

  • Anemias due to a lack of functional hemoglobin.
    Potential causes are
    • faulty or impaired formation of the globin chains of hemoglobin (e.g. thalassemia, sickle-cell disease),
    • disorders of the iron metabolism (congenital forms of iron deficiency anemia, congenital and acquired forms of iron overload, e.g. juvenile hemochromatosis),
    • chronic inflammatory disease (anemia of chronic disease, chronic anemia of infection),
    • premature breakdown of red blood cells (hemolytic anemias: z.B. hereditary spherocytosis, autoimmune hemolytic anemias)
    • vitamin deficiency. 
  • Congenital and acquired aplastic anemias in which not all or no blood cells are formed in the bone marrow (e.g. Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome)
  • Hemostatic and coagulation disorders with a reduced number or impaired functioning of platelets (thrombocytopenia, thrombocytosis), lack or excess of coagulation factors (hemophilia / thrombophilia)
  • Acquired immunodeficiencies due to various disorders of the immune system (e.g. CVID/common variable immunodeficiency, SCID/severe combined immunodeficiency, chronic granulomatous disease).



Our patient-oriented research aims at continuously improving the diagnosis and treatment strategies of rare hematological disorders. To this end we examine the molecular causes of the individual disorders with the aim of identifying promising approaches for future therapies. We focus on regulatory mechanisms of the iron metabolism, the regulation of hemoglobin synthesis and the formation of important coagulation factors.

Our researchers cooperate closely with other departments of Heidelberg University Hospital, with the Opens external link in new windowCenter for Rare Diseases and with research groups of external institutions like the European Molecular Biology Laboratory (EMBL) in Heidelberg. We are a member of the National Genome Research Network (NGFN), of supraregional research networks of the German Research Foundation (DFG) and the European Union, and of the research network of the Federal Ministry of Education and Research (BMBF). In cooperation with our colleagues from Berlin, Frankfurt, Hamburg and Ulm, we direct the registry study for patients with sickle-cell disease of the Society for Pediatric Oncology and Hematology. We are also part of the Europe-wide Opens external link in new windowENERCA-network for rare anemias and contribute to the Opens external link in new windowInformation Portal on Blood and Coagulation Disorders in Children and Adolescents with our colleagues from the GPOH.

II.  Staff

Martina Muckenthaler

Joachim Kunz

Andreas Kulozik

and members of the Kulozik group and the Muckenthaler group.

III. Project funding

BMBF, "Towards improved diagnosis and treatment of rare inherited microcytic hypochromic anemias related to iron metabolism" (HMA-Iron), funding period: 2010 - 2013


Opens external link in new windowDietmar Hopp Foundation  Translational medicine of hereditary anemias, funding period 2010-2013



IV.  Publications


Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload.
Altamura S, Kessler R, Gröne HJ, Gretz N, Hentze MW, Galy B, Muckenthaler MU.
Cell Metab. 2014 Aug 5;20(2):359-67. doi: 10.1016/j.cmet.2014.07.007.


Human L-ferritin deficiency is characterized by idiopathic generalized seizures and atypical restless leg syndrome.
Cozzi A, Santambrogio P, Privitera D, Broccoli V, Rotundo LI, Garavaglia B, Benz R, Altamura S, Goede JS, Muckenthaler MU, Levi S.
J Exp Med. 2013 Aug 26;210(9):1779-91. doi: 10.1084/jem.20130315. Epub 2013 Aug 12.


Out of balance--systemic iron homeostasis in iron-related disorders.
Steinbicker AU, Muckenthaler MU.
Nutrients. 2013 Aug 2;5(8):3034-61. doi: 10.3390/nu5083034. Review.


Iron deficiency anaemia and cataracts in a patient with haemochromatosis.
Peiffer KH, Niemeyer M, Buslau A, Kohnen T, Muckenthaler MU, Zeuzem S, Sarrazin C.
Gut. 2014 Apr;63(4):686, 698. doi: 10.1136/gutjnl-2013-305049. Epub 2013 Jul 18. No abstract available.


Iron refractory iron deficiency anemia.
De Falco L, Sanchez M, Silvestri L, Kannengiesser C, Muckenthaler MU, Iolascon A, Gouya L, Camaschella C, Beaumont C.
Haematologica. 2013 Jun;98(6):845-53. doi: 10.3324/haematol.2012.075515. Review.


Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome.
Luscieti S, Tolle G, Aranda J, Campos CB, Risse F, Morán É, Muckenthaler MU, Sánchez M.
Orphanet J Rare Dis. 2013 Feb 19;8:30. doi: 10.1186/1750-1172-8-30.


Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients.
Lehmberg K, Grosse R, Muckenthaler MU, Altamura S, Nielsen P, Schmid H, Graubner U, Oyen F, Zeller W, Schneppenheim R, Janka GE.
Ann Hematol. 2013 Mar;92(3):387-94. doi: 10.1007/s00277-012-1618-8. Epub 2012 Nov 20.

The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice.
Casanovas G, Vujić Spasic M, Casu C, Rivella S, Strelau J, Unsicker K, Muckenthaler MU.
Haematologica. 2013 Mar;98(3):444-7. doi: 10.3324/haematol.2012.069807. Epub 2012 Sep 14.


Smad6 and Smad7 are co-regulated with hepcidin in mouse models of iron overload.
Vujić Spasić M, Sparla R, Mleczko-Sanecka K, Migas MC, Breitkopf-Heinlein K, Dooley S, Vaulont S, Fleming RE, Muckenthaler MU.
Biochim Biophys Acta
. 2013 Jan;1832(1):76-84. doi: 10.1016/j.bbadis.2012.08.013. Epub 2012 Aug 31.


Hfe deficiency impairs pulmonary neutrophil recruitment in response to inflammation.
Benesova K, Vujić Spasić M, Schaefer SM, Stolte J, Baehr-Ivacevic T, Waldow K, Zhou Z, Klingmueller U, Benes V, Mall MA, Muckenthaler MU.
PLoS One. 2012;7(6):e39363. doi: 10.1371/journal.pone.0039363. Epub 2012 Jun 21.


Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II.
Casanovas G, Swinkels DW, Altamura S, Schwarz K, Laarakkers CM, Gross HJ, Wiesneth M, Heimpel H, Muckenthaler MU.
J Mol Med (Berl). 2011 Aug;89(8):811-6. doi: 10.1007/s00109-011-0751-5. Epub 2011 Apr 8.


The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice.
Castoldi M, Vujic Spasic M, Altamura S, Elmén J, Lindow M, Kiss J, Stolte J, Sparla R, D'Alessandro LA, Klingmüller U, Fleming RE, Longerich T, Gröne HJ, Benes V, Kauppinen S, Hentze MW, Muckenthaler MU.
J Clin Invest
. 2011 Apr;121(4):1386-96. doi: 10.1172/JCI44883.


A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA.
Altamura S, D'Alessio F, Selle B, Muckenthaler MU.
Biochem J. 2010 Nov 1;431(3):363-71. doi: 10.1042/BJ20100668.


Two to tango: regulation of Mammalian iron metabolism.
Hentze MW, Muckenthaler MU, Galy B, Camaschella C.
Cell. 2010 Jul 9;142(1):24-38. doi: 10.1016/j.cell.2010.06.028. Review.


Hyperferritinaemia-cataract syndrome: worldwide mutations and phenotype of an increasingly diagnosed genetic disorder.
Millonig G, Muckenthaler MU, Mueller S.
Hum Genomics. 2010 Apr;4(4):250-62. Review.


Heme controls ferroportin1 (FPN1) transcription involving Bach1, Nrf2 and a MARE/ARE sequence motif at position -7007 of the FPN1 promoter.
Marro S, Chiabrando D, Messana E, Stolte J, Turco E, Tolosano E, Muckenthaler MU.
Haematologica. 2010 Aug;95(8):1261-8. doi: 10.3324/haematol.2009.020123. Epub 2010 Feb 23.

[Hereditary hyperferritinemia cataract syndrome--the first family in Germany].
Millonig G, Holzer MP, Tolle G, Auffarth GU, Muckenthaler MU, Seitz HK, Mueller S.
Z Gastroenterol. 2009 Dec;47(12):1211. doi: 10.1055/s-0028-1109523. German.


SELDI-TOF MS detection of urinary hepcidin.
Altamura S, Kiss J, Blattmann C, Gilles W, Muckenthaler MU.
Biochimie. 2009 Oct;91(10):1335-8. doi: 10.1016/j.biochi.2009.04.010. Epub 2009 Apr 22.