title: Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation.
abstract: Congenital dyserythropoietic anemia type I (CDA I) is a rare autosomal recessive disorder with ineffective erythropoiesis and iron overloading. More than 100 cases have been described, but with the exception of a report on a large Bedouin tribe, these reports include only small numbers of cases, and no data on the lifetime evolution of the disease are available. Since 1967, we have been able to follow 21 cases from 19 families for up to 37 years. Twenty-one patients with a confirmed diagnosis of CDA I exhibited chronic macrocytic anemia of variable severity, requiring regular red cell transfusions only in 2 individuals. Four developed gallstones before the age of 30 years. Fifteen of 16 cases alive at the time of analysis showed mutations of at least one allele from exons 6 to 28 within CDAN1. Iron overloading is to be expected in all patients. In 9 patients, iron depletion was started between the ages of 7 and 36 years. Splenectomy, which was performed in 7 patients, did not result in improvement of hemoglobin values. Five patients were treated with interferon alpha-2a, and all responded with a rise in hemoglobin concentration of between 25 and 35 g/L (2.5 and 3.5 g/dL) starting within 4 weeks.
authors.affiliation: Department of Internal Medicine III, University of Ulm, Germany, Robert Koch Strasse 8, D-89081 Ulm, Germany. hermann.heimpel@medizin.uni-ulm.de
authors.forename: Hermann
authors.initials: H
authors.lastname: Heimpel
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Monika
authors.initials: M
authors.lastname: Ebnöther
authors.forename: Jeroen S
authors.initials: JS
authors.lastname: Goede
authors.forename: Detlev
authors.initials: D
authors.lastname: Heydrich
authors.forename: Torsten
authors.initials: T
authors.lastname: Kamp
authors.forename: Lothar
authors.initials: L
authors.lastname: Plaumann
authors.forename: Bettina
authors.initials: B
authors.lastname: Rath
authors.forename: Jochen
authors.initials: J
authors.lastname: Roessler
authors.forename: Otto
authors.initials: O
authors.lastname: Schildknecht
authors.forename: Mathias
authors.initials: M
authors.lastname: Schmid
authors.forename: Walter
authors.initials: W
authors.lastname: Wuillemin
authors.forename: Beate
authors.initials: B
authors.lastname: Einsiedler
authors.forename: Rosi
authors.initials: R
authors.lastname: Leichtle
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kohne
mesh_terms: D000293:Adolescent; D000328:Adult; D000742:Anemia, Dyserythropoietic, Congenital / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000748:Anemia, Macrocytic; D002648:Child; D005091:Exons; D005192:Family Health; D005260:Female; D042882:Gallstones; D005858:Germany / Q000453:epidemiology; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007501:Iron / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D011379:Prognosis; D011994:Recombinant Proteins; D013156:Splenectomy
chemical_list: C470477:CDAN1 protein, human; D006023:Glycoproteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D007501:Iron