Case Report: A Turkish family with congenital dyserytropoietic anaemia type II
Wiebers, S., Maanen, T.M. van, Meijer, W.G.
Voorzitter(s): mw. prof.dr. J. de Graaf, Nijmegen & mw. dr. E.J.M. Mattijssen, Arnhem
Locatie(s): Auditorium 2
Categorie(ën):
Introduction: Congenital hemolytic anemias are classified by causative mechanism. The most common types are genetic conditions of the red bloodcell (RBC) membrane (heriditairy spherocytosis, heriditairy elliptocytosis, heriditairy pyropoikilocytosis, heriditairy stomatocytosis), enzyme defects of the RBC (glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency) or hemoglobinopathies (sickle cell anemia, thalassemia). We report on a family with a rare heriditary hemolytic anemia due to congenital dyserythropoietic anemia (CDA) type II.
Case report: A 37-year old man was admitted for right upper quadrant abdominal pain, dark urine and discolored stools. His medical history reported M. Bechterew and a mild congenital hemolytic anaemia, not further specified. The patients family is of Turkish background. Two of his sisters (eight siblings) were also diagnosed with hemolytic anaemia. On physical examination there was jaundice and upper abdominal tenderness, vital signs were normal. Laboratory results showed hemoglobin 8.0 mmol/l, mean corpuscular volume 87 fl, platelets 148* 10⁹/l, leukocytes 6.5* 10⁹/l, blood smear showed no abnormalities, C-reactive protein 2mg/l, reticulocytes 13 promille, haptoglobin < 0.10 g/l, alkaline phosphatase 142U/l, gamma-glutamyltransferase 326 U/l, bilirubine conjugated 253 µmol/l, billirubin unconjugated 176 µmol/l, aspartate transaminase 185 U/l, alanine transaminase 279 U/l, lactate dehydrogenase 195 U/l, ferritin 1196 µg/l. Ultrasound showed choledocholithiasis and splenomegaly. On endoscopic retrograde cholangiopancreatography bile ducts were not dilated and no concrements were visualized. A transient gallstone seemed the most probable cause.
Further tests were performed to investigate the cause of the hemolytic anemia. Enzymedeficiencies were absent. Hb-electrophoresis showed no evidence for a hemoglobinopathy. Hereditary spherocytosis (HS) was not ruled out: BAND 3 expression was just below the cut-off value, however spectrine percentage was normal. A bone marrow biopsy showed dyserythropoiesis with multinucleated erytroblasts and chromatin bridges. There was a homozygote SEC23B mutation.
Conclusion: This patient was admitted for choledocholithiasis due to hemolysis caused by CDA type II based on homozygote SEC23B mutation. Two sisters of our patient are probably affected as well. CDA type II is a rare disorder with autosomale recessive inheritance, leading to ineffective erytropoiesis. Chromatin bridges are in most cases described in CDA type I. A SEC23B mutation is associated with hypoglycosylation of BAND3 in vivo. CDA is often misdiagnosed as hemolytic anemia, thalassemia or hereditary spherocytosis. Iron overload is a common problem in CDA, this explains the high ferritin level in our patient.