Acta Paediatr 81: 652-3. 1992
CASE REPORT
Congenital sideroblastic anaemia with intrauterine symptoms and early lethal outcome K Andersen and PH Kaad Department of Paediatrics, Hjerring Hospital, Hjerring, Denmark
Andersen K, Kaad PH.Congenital sideroblastic anaemia with intrauterine symptoms and early lethal outcome. Acta Paediatr 1992;8I :652-3. Stockholm. ISSN 0803-5253 Sideroblastic anaemia is a rare disease, which most often presents in early childhood. A case of ringed sideroblastic anaemia with onset in early foetal life in a female infant, resulting in severe intrauterine symptoms, is reported. Six weeks after birth a bone marrow examination revealed a large amount of typical ringed sideroblasts, thus establishing the diagnosis. In spite of repeated blood transfusions, the haemoglobin content gradually decreased. The condition was refractory to pyridoxal phosphate treatment and continued to deteriorate with lethal outcome four months after birth. 0 Intrauterine symptoms, pyridoxal phosphate, sideroblastic anaemia K Andersen, Department of Paediatrics, Hjarring Hospital, DK-9800 Hjarring. Denmark
Congenital sideroblastic anaemia is a rare disease, representing approximately 1YO of all anaemic conditions in the neonate. The disease is characterized by abnormal iron metabolism and is associated with hypochromic, microcytic anaemia and bone marrow erythroid hyperplasia, ringed sideroblasts constituting 1040% of the nucleated bone marrow cells. This erythrocytic precursor is a normoblast containing excessive amounts of mitochondria1 iron in a characteristic perinuclear pattern. The causes of sideroblastic anaemia are heterogeneous. Decreased delta aminolaevulinic acid synthase and haeme synthase activities have been observed frequently, but so far abnormal or absent haeme synthesis enzymes have not been proved as the primary abnormality (1, 2). The anaemia may be evident at birth or during infancy, but the disease most often presents in early childhood (3). We report a case of congenital ringed sideroblastic anaemia in a female infant showing severe intrauterine symptoms, with an early lethal outcome. To our knowledge, this is the first case of sideroblastic anaemia with intrauterine symptoms reported in the literature.
Case report The female infant was born by caesarean section after 34 weeks’ gestation. The mother had given birth to two children previously, and the actual pregnancy was uncomplicated until the 28th week of gestation, when ultrasound scanning revealed a foetus with hydroperi-
cardium and enlarged liver. Haemoglobin concentration was 2.4 mmol/l(38.7 g/l). The mother’s blood tests showed no signs of infection or haemolytic anaemia. Intrauterine blood transfusions were given, and the child was delivered by caesarean section six weeks before term. The newborn female revealed no malformations and had a normal chromosomal pattern. Birth weight was 2155 g, capillary haemoglobin content was 6.9 mmol/l (1 1 1 g/l), bilirubin 83 mmol/l and the reticulocyte count 53%. She was treated for minor respiratory insufficiency and cardiac incompensation. Replacement blood transfusion was given at birth, and whole blood transfusions were given weekly thereafter; the haemoglobin level decreased gradually, however. Haemoglobin electrophoresis was normal. Blood tests showed no signs of bleeding or haemolytic anaemia. Peripheral blood film, total and differential white blood cell and platelet counts were normal. Ekhocardiography, ultrasound scanning of the liver, spleen and kidneys indicated no abnormalities. Six weeks after birth peripheral blood values showed haemoglobin 5.5 mmol/l (88 g/l), reticulocytic count 1.0%, MCV 90.7 fl, MCHC 20.3 mmol/l (327 g/l), red blood cells 3.7 x 10l2/1,white blood cells 11.0 x 109/1and platelets 534 x 109/l.The peripheral blood film showed slight anisocytosis and poikilocytosis, but no microcytic hypochromia. Bone marrow examination revealed a hyperplastic bone marrow, erythroid hypoplasia, erythroblasts constituting 10% of the nucleated cells. The myelopoiesis appeared normal, but very active. On iron-stained smears, more than 50% of the nucleated cells from the erythropoiesis consisted of ringed sideroblasts, confirming the diagnosis of ringed sideroblastic anaemia.
A C T A PEDIATR 81 (1992)
Sideroblastic anaemia
653
The patient was treated with oral pyridoxal phos- marrow examination at birth is unknown in sideroblasphate 50 mg/day, increasing to 200 mg/day, but the tic anaemia. anaemic condition did not improve. Apparently, our patient is the first female reported to A new bone marrow aspirate, performed three have developed the disease in early foetal life, the months after birth, was hypercellular with increased diagnosis having been made six weeks after. birth erythropoiesis, normal thrombopoiesis and granulo- through a bone marrow examination. At that time a poiesis. The aspirate showed a moderate increase in the peripheral blood film showed minor abnormalities and iron content. On iron-stained smears a high proportion the peripheral blood values of erythrocytic MCV and of ringed sideroblasts was found. The peripheral blood MCHC were normal, probably due to several blood film showed marked anisocytosis and poikilocytosis, transfusions. T o our knowledge a prenatal diagnosis of and hypochromia to a minor extent. The peripheral sideroblastic anaemia was never made. Sideroblastic anaemia has a variable clinical course, blood values showed normal MCV and MCHC values. Metabolic screening revealed no abnormal condi- and may lead to death in infancy. The average survival is tions, especially as regards tryptophan metabolism. approximately five years from the onset of anaemia, Generally, the clinical condition was poor and conti- death usually resulting from cardiac arrhythmias, liver nued to deteriorate in spite of blood transfusions every and bone marrow failure, or infection. However, second week. The condition was further aggravated by patients that respond well to pyridoxal phosphate recurrent diarrhoea, cardiac incompensation and septi- treatment may live comfortably for many years. caemia with high temperature and leucocytosis. We Our patient had an extremely short clinical course, found no cause for the diarrhoea. Exocrine pancreatic being completely resistant to pyridoxal phosphate treatfunction was not examined. The patient gradually ment. The response to pyridoxal phosphate varies became exhausted and died at four months of age in a considerably from complete recovery to no response. In state of dehydration and cardiac incompensation. The less than half of the cases reported, a positive response is obtained. There are no distinct clinical, haematological parents did not authorize an autopsy. Blood tests and peripheral blood films showed that or biochemical differences between pyridoxal phosphate both parents and an elder brother were healthy with no responsive and refractory cases (1, 3, 5). Pyridoxal signs of anaemia. However, in 1981, a male sibling was phosphate should therefore be given in all cases, and the born by caesarean section after 35 weeks’ gestation. He normal dosage is 50 to 200 mg/day (1, 3, 5). The treatment of the carrier mother with pyridoxal was extremely anaemic with a haemoglobin content of 2.8 mmol/l (45 g/l), dysmature with a birth weight of phosphate may have a curative effect on the foetus. The only alternative to pyridoxal phosphate treat1470 g and suffering from severe cardiac insufficiency. He died 2 h after birth showing no signs of haemolytic ment is symptomatic blood transfusion. Haem arginate disease, bleeding or erythroblast leukemia. Bone mar- infusions may improve the condition in patients with row examination revealed a few scattered sideroblasts, congenital sideroblastic anemia by normalizing the but no typical ringed sideroblasts. haeme synthesizing enzyme activity (6), but this is still in the experimental stage. Anaemia in the neonate is most often haemolytic, only rarely because of bleeding, and almost never due to defective erythropoiesis. This condition, however, must Discussion be kept in mind when treating neonates suffering from In the majority of cases, when a patient suffers a severe anemia. congenital ringed sideroblastic anaemia, an X-linked recessive inheritance pattern can be demonstrated; males show anaemia whereas female carriers experience mild morphological changes of the red cells combined References with an increase in serum iron values (1, 2). However, I . Manabe Y, Set0 S. Furusho K, Aoki Y. A study of a female with congenital sideroblastic anemia. Am J Hematol 1982;12:63-7 more severe cases have been recognized in females also 2. Holmes J, May A, Geddes D, Jacobs A. A family study of (1, 3,4). In some families a recessive autosomal pattern congenital X linked sideroblastic anaemia. J Med Genet 1990; of inheritance is evident (4, 5). In our case the severe 27126-8 symptoms combined with clinically and haematologi- 3. Agarwal MB. Congenital sideroblastic anemia in a female. Indian Pediatr 1988;25:685-8 cally normal parents suggest that the patient was Kasturi J, Basha HM, Smeda SH, Swehli M. Hereditary Siderohomozygous and suffered an autosomal recessive defect. 4. blastic anemia in 4 siblings of a Libyan family-autosomal This idea is supported by the fact that an elder brother inheritance. Acta Haematol (Bristol) 1982;68:321-4 was born prematurely with the same clinical and 5. Amos RJ, Miller ALC, Amess JAL. Autosomal inheritance of sideroblastic anaemia. Clin Lab Haematol 1988;10:347-53 haematological features, resulting in death 2 h after birth. However, the examination of the brother’s bone 6. Volin L. Haem arginate treatment for hereditary sideroblastic anaemia. Eur J Haematol 1989;42:60-6 marrow did not reveal any typical signs of ringed sideroblasts. However, the diagnostic value of a bone Received April 8, 1991. Accepted Nov. 20, 1991
CASE REPORT
Congenital sideroblastic anaemia with intrauterine symptoms and early lethal outcome K Andersen and PH Kaad Department of Paediatrics, Hjerring Hospital, Hjerring, Denmark
Andersen K, Kaad PH.Congenital sideroblastic anaemia with intrauterine symptoms and early lethal outcome. Acta Paediatr 1992;8I :652-3. Stockholm. ISSN 0803-5253 Sideroblastic anaemia is a rare disease, which most often presents in early childhood. A case of ringed sideroblastic anaemia with onset in early foetal life in a female infant, resulting in severe intrauterine symptoms, is reported. Six weeks after birth a bone marrow examination revealed a large amount of typical ringed sideroblasts, thus establishing the diagnosis. In spite of repeated blood transfusions, the haemoglobin content gradually decreased. The condition was refractory to pyridoxal phosphate treatment and continued to deteriorate with lethal outcome four months after birth. 0 Intrauterine symptoms, pyridoxal phosphate, sideroblastic anaemia K Andersen, Department of Paediatrics, Hjarring Hospital, DK-9800 Hjarring. Denmark
Congenital sideroblastic anaemia is a rare disease, representing approximately 1YO of all anaemic conditions in the neonate. The disease is characterized by abnormal iron metabolism and is associated with hypochromic, microcytic anaemia and bone marrow erythroid hyperplasia, ringed sideroblasts constituting 1040% of the nucleated bone marrow cells. This erythrocytic precursor is a normoblast containing excessive amounts of mitochondria1 iron in a characteristic perinuclear pattern. The causes of sideroblastic anaemia are heterogeneous. Decreased delta aminolaevulinic acid synthase and haeme synthase activities have been observed frequently, but so far abnormal or absent haeme synthesis enzymes have not been proved as the primary abnormality (1, 2). The anaemia may be evident at birth or during infancy, but the disease most often presents in early childhood (3). We report a case of congenital ringed sideroblastic anaemia in a female infant showing severe intrauterine symptoms, with an early lethal outcome. To our knowledge, this is the first case of sideroblastic anaemia with intrauterine symptoms reported in the literature.
Case report The female infant was born by caesarean section after 34 weeks’ gestation. The mother had given birth to two children previously, and the actual pregnancy was uncomplicated until the 28th week of gestation, when ultrasound scanning revealed a foetus with hydroperi-
cardium and enlarged liver. Haemoglobin concentration was 2.4 mmol/l(38.7 g/l). The mother’s blood tests showed no signs of infection or haemolytic anaemia. Intrauterine blood transfusions were given, and the child was delivered by caesarean section six weeks before term. The newborn female revealed no malformations and had a normal chromosomal pattern. Birth weight was 2155 g, capillary haemoglobin content was 6.9 mmol/l (1 1 1 g/l), bilirubin 83 mmol/l and the reticulocyte count 53%. She was treated for minor respiratory insufficiency and cardiac incompensation. Replacement blood transfusion was given at birth, and whole blood transfusions were given weekly thereafter; the haemoglobin level decreased gradually, however. Haemoglobin electrophoresis was normal. Blood tests showed no signs of bleeding or haemolytic anaemia. Peripheral blood film, total and differential white blood cell and platelet counts were normal. Ekhocardiography, ultrasound scanning of the liver, spleen and kidneys indicated no abnormalities. Six weeks after birth peripheral blood values showed haemoglobin 5.5 mmol/l (88 g/l), reticulocytic count 1.0%, MCV 90.7 fl, MCHC 20.3 mmol/l (327 g/l), red blood cells 3.7 x 10l2/1,white blood cells 11.0 x 109/1and platelets 534 x 109/l.The peripheral blood film showed slight anisocytosis and poikilocytosis, but no microcytic hypochromia. Bone marrow examination revealed a hyperplastic bone marrow, erythroid hypoplasia, erythroblasts constituting 10% of the nucleated cells. The myelopoiesis appeared normal, but very active. On iron-stained smears, more than 50% of the nucleated cells from the erythropoiesis consisted of ringed sideroblasts, confirming the diagnosis of ringed sideroblastic anaemia.
A C T A PEDIATR 81 (1992)
Sideroblastic anaemia
653
The patient was treated with oral pyridoxal phos- marrow examination at birth is unknown in sideroblasphate 50 mg/day, increasing to 200 mg/day, but the tic anaemia. anaemic condition did not improve. Apparently, our patient is the first female reported to A new bone marrow aspirate, performed three have developed the disease in early foetal life, the months after birth, was hypercellular with increased diagnosis having been made six weeks after. birth erythropoiesis, normal thrombopoiesis and granulo- through a bone marrow examination. At that time a poiesis. The aspirate showed a moderate increase in the peripheral blood film showed minor abnormalities and iron content. On iron-stained smears a high proportion the peripheral blood values of erythrocytic MCV and of ringed sideroblasts was found. The peripheral blood MCHC were normal, probably due to several blood film showed marked anisocytosis and poikilocytosis, transfusions. T o our knowledge a prenatal diagnosis of and hypochromia to a minor extent. The peripheral sideroblastic anaemia was never made. Sideroblastic anaemia has a variable clinical course, blood values showed normal MCV and MCHC values. Metabolic screening revealed no abnormal condi- and may lead to death in infancy. The average survival is tions, especially as regards tryptophan metabolism. approximately five years from the onset of anaemia, Generally, the clinical condition was poor and conti- death usually resulting from cardiac arrhythmias, liver nued to deteriorate in spite of blood transfusions every and bone marrow failure, or infection. However, second week. The condition was further aggravated by patients that respond well to pyridoxal phosphate recurrent diarrhoea, cardiac incompensation and septi- treatment may live comfortably for many years. caemia with high temperature and leucocytosis. We Our patient had an extremely short clinical course, found no cause for the diarrhoea. Exocrine pancreatic being completely resistant to pyridoxal phosphate treatfunction was not examined. The patient gradually ment. The response to pyridoxal phosphate varies became exhausted and died at four months of age in a considerably from complete recovery to no response. In state of dehydration and cardiac incompensation. The less than half of the cases reported, a positive response is obtained. There are no distinct clinical, haematological parents did not authorize an autopsy. Blood tests and peripheral blood films showed that or biochemical differences between pyridoxal phosphate both parents and an elder brother were healthy with no responsive and refractory cases (1, 3, 5). Pyridoxal signs of anaemia. However, in 1981, a male sibling was phosphate should therefore be given in all cases, and the born by caesarean section after 35 weeks’ gestation. He normal dosage is 50 to 200 mg/day (1, 3, 5). The treatment of the carrier mother with pyridoxal was extremely anaemic with a haemoglobin content of 2.8 mmol/l (45 g/l), dysmature with a birth weight of phosphate may have a curative effect on the foetus. The only alternative to pyridoxal phosphate treat1470 g and suffering from severe cardiac insufficiency. He died 2 h after birth showing no signs of haemolytic ment is symptomatic blood transfusion. Haem arginate disease, bleeding or erythroblast leukemia. Bone mar- infusions may improve the condition in patients with row examination revealed a few scattered sideroblasts, congenital sideroblastic anemia by normalizing the but no typical ringed sideroblasts. haeme synthesizing enzyme activity (6), but this is still in the experimental stage. Anaemia in the neonate is most often haemolytic, only rarely because of bleeding, and almost never due to defective erythropoiesis. This condition, however, must Discussion be kept in mind when treating neonates suffering from In the majority of cases, when a patient suffers a severe anemia. congenital ringed sideroblastic anaemia, an X-linked recessive inheritance pattern can be demonstrated; males show anaemia whereas female carriers experience mild morphological changes of the red cells combined References with an increase in serum iron values (1, 2). However, I . Manabe Y, Set0 S. Furusho K, Aoki Y. A study of a female with congenital sideroblastic anemia. Am J Hematol 1982;12:63-7 more severe cases have been recognized in females also 2. Holmes J, May A, Geddes D, Jacobs A. A family study of (1, 3,4). In some families a recessive autosomal pattern congenital X linked sideroblastic anaemia. J Med Genet 1990; of inheritance is evident (4, 5). In our case the severe 27126-8 symptoms combined with clinically and haematologi- 3. Agarwal MB. Congenital sideroblastic anemia in a female. Indian Pediatr 1988;25:685-8 cally normal parents suggest that the patient was Kasturi J, Basha HM, Smeda SH, Swehli M. Hereditary Siderohomozygous and suffered an autosomal recessive defect. 4. blastic anemia in 4 siblings of a Libyan family-autosomal This idea is supported by the fact that an elder brother inheritance. Acta Haematol (Bristol) 1982;68:321-4 was born prematurely with the same clinical and 5. Amos RJ, Miller ALC, Amess JAL. Autosomal inheritance of sideroblastic anaemia. Clin Lab Haematol 1988;10:347-53 haematological features, resulting in death 2 h after birth. However, the examination of the brother’s bone 6. Volin L. Haem arginate treatment for hereditary sideroblastic anaemia. Eur J Haematol 1989;42:60-6 marrow did not reveal any typical signs of ringed sideroblasts. However, the diagnostic value of a bone Received April 8, 1991. Accepted Nov. 20, 1991
