Int. Med J Vol 4 No 2 December 2005

Sideroblastic Anaemia In A Malay Family 

Marini R, W. Zaidah W.A, Suhair A., Rosline H

Department Of Hematology, School Of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan;

ABSTRACT    

Three cases of sideroblastic anaemia diagnosed from one family were described. A 41-year old Malay mother had been reported as having primary acquired sideroblastic anaemia : Refractory anaemia with ring sideroblasts (RARS) from bone marrow aspirate during her first pregnancy. The diagnosis was made because there was no history of anaemia at younger age, no family history of anaemia and no identifiable secondary causes were recognised. Ten years later it was discovered that two of her children, also developed refractory anaemia and were diagnosed as sideroblastic anaemia. Hence, the initial diagnosis of the acquired sideroblastic anaemia had been reviewed because there were more than one person in the family who were affected. The diagnosis of hereditary sideroblastic anaemia was the most probable. Investigations such as enzyme assay and DNA analysis are required to further sub-classifiey this disorder. These cases emphasize the importance of evaluating all cases suspected of acquired disorder RARS for pyridoxine responsiveness to exclude hereditary form.

Keyword : Hereditary sideroblastic anaemia, Pyridoxine-responsive sideroblastic anaemia

INTRODUCTION

Sideroblastic anaemias comprise of a heterogenous group of refractory anaemias characterized by the presence of anaemia, low reticulocyte count and ineffective erythropoiesis¹. The key for diagnosis is the presence of 15% ring sideroblast in erythroid precursors of bone marrow aspirate. It can be classified as acquired or hereditary type. The acquired form is more common². It can be idiopathic or caused by drugs, toxins and certain diseases such as myelodysplastic syndrome. The anaemia normally manifests later in life². The hereditary form could be either X-linked or autosomal inheritance. The commonest form is X-linked. Here, we report a case of a mother who was earlier diagnosed as primary acquired disorder RARS. This previous diagnosis in the mother had been reviewed in this report, becauset two of her children were also diagnosed as sideroblastic anaemia later. Though primary acquired RARS is more common, the diagnosis of hereditary type needs to be excluded by doing anaemia work-up and follow-ups for the whole family.

CASE REPORT

A 41-year-old mother was diagnosed as primary acquired sideroblastic anaemia in 1988 during her first pregnancy. At that time she presented with severe anaemia (Hb 4.3g/dl, MCV 95.8 fl) for which she received red cells transfusion and haematinics. There was no significant past medical and drug history. There was also no family history of anaemia. On examination, there was no hepatosplenomegaly.  Her peripheral blood film showed normochromic normocytic anaemia with anisocytosis and bone marrow revealed marked erythroid hyperplasia showing dyserythropoeitic features and 17% ring sideroblasts. Reticulocytes count was 0.2%. White blood cells and platelet counts were within normal ranges. Serum ferritin was raised (510mg/l) with normal levels of serum folate and vitamin B12. Other investigations such as renal and liver function tests, haemoglobin (Hb) electrophoresis and glucose-6-phosphate dehydrogenase screening were normal. Postnatally she had another episode of severe anaemia (Hb 4.5g/dl, MCV 113fl) requiring red cells transfusion. Following that, there was spontaneous improvement in her haemoglobin level and then she was lost to follow-up. Five years later she presented again during her third pregnancy with a similar complaint.     

Her first son presented with recurrent anaemia since he was three years of age and was admitted several times to hospital for red cells transfusion. No history of jaundice, passing tea colored urine or taking any drugs. At that time his baseline haemoglobin was 7g/dl. Reticulocytes count was 0.2%.  Peripheral blood film revealed a dimorphic blood picture showing hypochromic microcytic cells and macrocytes with occasional basophilic stippling. Hb eletrophoresis was normal. Serum ferritin was 367mg/L. Patient was known to be G6PD deficient. Viral study was negative. His parents refused further investigations until the year 2003 when he was 15 years of age; bone marrow aspirate was performed and revealed sideroblastic anaemia with presence of 15% ring sideroblasts (Fig:1) and erythroid hyperplasia with underlying dyserythropoeisis with the presence of binucleated normoblast, intercytoplasmic bridging and basophilic stippling.

The second daughter presented with recurrent anaemia requiring regular red cells transfusion since she was three years of age. At that time her baseline haemoglobin level was 6.1g/dl. Peripheral blood film showed normocytic normochromic anaemia. Reticulocytes count was 1.0%. Bone marrow aspirate revealed erythroid hyperplasia with dyserythropoeisis and presence of ring sideroblasts. She was diagnosed as having HbE trait (most likely inherited from her father) and her serum ferritin was 87.8µg/L.

Both siblings were under regular hospital follow-up since 2000 and were taking folic acid (5mg/daily) and pyridoxine tablet (40mg/daily). Their haemoglobin levels significantly improved between 10-11 g/dl with continuous oral pyridoxine intake.            

DISCUSSION

In this case, the mother was initially diagnosed as having primary acquired sideroblastic anaemia because of several reasons; the patient is a female, with no history of anaemia at childhood and her peripheral blood film showed a macrocytic anaemia and returning to normal when she was not pregnant. There were no identifiable secondary causes. Hence, she was diagnosed as primary acquired sideroblastic anaemia.

Relapse during pregnancy may have been due to increased demand for red cell production³. The requirement for pyridoxine is markedly increased during pregnancy. The pyridoxine responsiveness could not be assessed in this patient, as pyridoxine therapy was not given. The diagnosis of primary acquired sideroblastic anaemia made previously need to be reviewed now because two other family members are affected by the same condition. It is most likely that the sideroblastic anaemia in this family was an inherited disorder. In addition both of the children had hypochromic microcytic anaemia and responding well to pyridoxine treatment. In some patients, particularly with the hereditary type, there is a response to pyridoxine therapy.

Hereditary sideroblastic anaemia is a disease with hypochromic and microcytic anaemia, except in a very rare syndrome such as Pearson’s syndrome where the presentation is macrocytic anaemia, which usually presents in infancy and it is rapidly fatal⁴. The commonest type of inherited disorder is X-linked sideroblastic anaemia (XLSA) however it is unlikely for this family because both genders were equally affected. Rarely, some women can be affected by XLSA however they normally present later in life due to loss of clones expressing the normal alleles on the X-chromosome⁴. However, this needs to be confirmed by proper family studies and DNA analysis. DNA sequencing will confirm delta-amino levulinic acid synthase-2 (ALAS-2) gene mutation on the X chromosome in diagnosing XLSA². The identification of ALAS-2 gene mutation has an important role in patients’ management because XLSA does not progress to leukaemia⁴. The other rare type of hereditary sideroblastic anaemia is an autosomal inheritance which was the most likely diagnosis for this family

In conclusion, although hereditary sideroblastic anaemia is a rare condition, the diagnosis should be considered when more than one member of the family is affected. Trial of pyridoxine treatment to assess responsiveness is important to be evaluated in all cases of sideroblastic anaemia.  

REFERENCES

1.         Bottomley SS. Sideroblastic anaemia. Clin Haematol. 1982 Jun;11(2):389-409. Review

2.         Alcindor Thierry, Bridges, Kenneth R. Sideroblastic anemia (review). Br J Haematol 2002; 116:733-743

3.         Cazzola M, May A, Bergamaschi G, Cerani P, Rosti V, Bishop DF. Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anaemia in carrier females. Blood  2000; 96, 4363-4365. 

4.         Cotter PD, May A, Fitzsimons EJ, Houstan T, Woodcock BE, al-Sabah AI, Wong L, Bishop DF. Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. J Clin Invest. 1995; 96(4), 2090-2096.

Correspondence:

Dr Rosline Hassan,

Department of Haematology,

School of Medical Sciences,

University Sains Malaysia,

16150 Kubang Kerian,

Kelantan, Malaysia.

e.mail : roslin@kb.usm.my

tel. no : +609-7664139

Fax no : +609-7653370