Discussion
Sideroblastic anaemia comprise a wide spectrum of relatively uncommon congenital and acquired disorder of erythropoiesis that are due to various abnormalities in heme synthesis and mitochondrial function. The characteristic feature that typifies all forms of sideroblastic anemia is the presence of ring sideroblasts in the bone marrow aspirate [1].
Congenital SA can be further sub -classified into syndromic and non-syndromic. Non syndromic includes: X-linked (XLSA), Mitochondrial transporter SLC25A38 defects SA, Mitochondrial heat shock pt 70 (HSPA9) defects SA, Mitochondrial heat shock cognate pt 20 (HSCB) defects SA, Glutaredoxin 5 deficiency and Erythropoietic protoporphyria . While syndromic SA include: X-linked with ataxia (XLSA/A), Sideroblastic anemia, B cell immunodeficiency, periodic fevers, and developmental delay (SIFD), Myopathy, lactic acidosis, and sideroblastic anemia (MLASA), and variants, Pearson marrow-pancreas syndrome and Thiamine responsive megaloblastic anemia (TRMA) [ 8-12]. Most of congenital SA are usually hypochromic microcytic with decreased MCV reflecting a reduction of heme synthesis in the erythroid precursors.
Acquired clonal SA include two MDS category; MDS with ring sideroblasts and single lineage dysplasia (MDS-RS-SLD), and MDS with ring sideroblasts and multilineage dysplasia (MDS-RS-MLD) and third category within the MDS/MPN neoplasm; myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)[4]. The anemia in these cases is usually normocytic or macrocytic, with a variable population of hypochromic cells on the peripheral blood smear.
Acquired SA from reversible causes (non-clonal) is similarly linked to mechanisms of impaired heme biosynthesis and accumulation of siderosomes. It has a very diverse etiology and may requires extensive investigation to elicit the cause that may include copper deficiency, drugs, lead toxicity, alcohol use, hypothermia, pyridoxine deficiency, or chronic neoplastic disease
Copper is an essential cofactor for the mitochondrial redox enzyme superoxide dismutase and reduced activity of this enzyme can lead to mitochondrial iron accumulation. Deficiency of copper can happen in many conditions such as reduced oral intake, malabsorption in the setting of gastrointestinal surgery and small bowel disorders or excessive gastrointestinal or urinary losses of copper. hypocupremia due to reduced copper absorption from the gastrointestinal tract can result as well from prolonged and excessive exposure to zinc. The anemia typically is normocytic or slightly macrocytic and the bone marrow usually show vacuolization of erythroid and myeloid precursors,
excessive stainable iron in plasma cells and macrophages in addition to the ring sideroblasts. Heavy metal toxicity, specifically from lead poisoning or zinc overdose is associated with SA. Excess exposure to zinc can cause SA by competing with iron incorporation into protoporphyrin and preventing intestinal absorption of copper through induction of an intestinal metal-binding protein metallothionein [13].
Although chloramphenicol and isoniazid and have been the prototypical drugs that cause SA, a list of other agents are implicated such as cycloserine, pyrazinamide, linezolid, fusidic acid, busulfan, melphalan, penicillamine, and Linezolid [7].
Pyridoxal phosphate the active form of vitamin B6 play essential role for ALAS2 enzymatic activity, that catalyze the condensation of glycine and succinyl coenzyme A to form 5-aminolevulinic acid (ALA), the first and rate-controlling enzyme of heme synthesis. Therefore, severe deficiency in vitamin B6 due to malnutrition or malabsorption, alcohol consumption or medication like INH can lead to SA.
Most of acquired non clonal SA associated with normal or increased MCV, except of INH toxicity [14].
During pregnancy anemia is a common problem. It can occur as part of physiological changes in pregnancy (dilutional anemia is part of normal pregnancy physiology, and there is a relative or absolute reduction in Hb concentration). However, the most common true anemia during pregnancy is iron deficiency anemia (IDA) encountered in around 75% of the cases. Other causes of anemia might include folate deficiency megaloblastic anemia [15]. Anemia affects approximately 30 percent of reproductive-age females and 40 percent of pregnant individuals, mostly due to iron deficiency. Pregnant women should be screened for anemia at booking visit and at 28 weeks Recurrent anemia during pregnancy can occur due to any of the aforementioned causes. Pure red aplasia (PRCA) can happen during pregnancy as well and it’s reported to recurs. Interestingly it’s reported to have spontaneous recovery after delivery [16].
Severe anemia may have adverse effects on the mother and the fetus. Anemia with hemoglobin levels less than 6 gr/dl is associated with increased risk for post postpartum hemorrhage, poor pregnancy outcome, preterm labor, Prematurity, spontaneous abortions, low birth weight, and fetal deaths are complications of severe maternal anemia and thus it is critical to distinguish iron deficiency anemia from physiologic anemia, as well as to identify other less common causes of anemia that may require treatment.
The World Health Organization (WHO) defines anemia as a hemoglobin level <11 g/dL (approximately equivalent to a hematocrit <33 percent) in the first trimester, <10.5 g/dL in the second trimester, <10.5 to 11 g/dL in the third trimester, or <10 g/dL postpartum. [17-21].
In our literature search, we came across very limited reports on sideroblastic anaemia in pregnancy, mostly as case reports that have shown the relationship between the toxic effect of orally administered sex hormone or pregnancy alone, and secondary sideroblastic anaemia [22-27].
All of the above were thought of within the differential diagnosis as a possible cause for the anaemia in the current reported case and were thoroughly investigated. Absence of family history, dysplasia andSF3B1 mutation and strict association of the anaemia with pregnancy, make CSA and clonal SA unlikely in our case. Likewise, the normal results for copper, zinc and lead with the absence of history of alcoholism or medication that linked to SA, exclude these acquired causes. The low pyridoxin level was implicated as the cause for the recurrent anaemia because of increased requirement during pregnancy.