Introduction
Sideroblastic anemia (SA) are a diverse group of disorders that characterized by anemia of varying severity and unified pathologically by an abnormal accumulation of iron in the mitochondria of the red cells precursors with impaired heme synthesis. The singular feature that characterize all forms of SA and is required for initial diagnosis is the presence iron-laden mitochondria forming a perinuclear ring around the nucleus of the erythroblast, visualized by Prussian blue staining of the bone marrow aspirate smear [1]. To be designated as ring sideroblasts, International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS) recommended that ring sideroblasts should have a minimum of 5 granules in a perinuclear distribution; these granules could either surround the entire nucleus, be localized to portions of the perinuclear area, or cover at least one third of the nucleus [2].
The unique pathology in SA can be primarily linked to defect in the heme biosynthesis, Fe-S biogenesis pathways as well as impaired synthesis of mitochondrial and cytosolic proteins essential for heme synthesis. These defects end in the build-up of iron granules rather than the normal incorporation of iron into the protoporphyrin IX (PPIX) in the mitochondrion [3].
Sideroblastic anaemia conventionally classified into congenital (CSA) or acquired (ASA). CSA is rare and caused by germline mutation affecting a nuclear or mitochondrial gene involved in three mitochondrial pathways: Heme biosynthesis, Iron-sulfur cluster and Mitochondrial protein synthesis and respiration. It is characterized by a heterogeneous pattern of inheritance; X-linked (XLSA), autosomal recessive (ARCSA), or Mitochondrially inherited forms. The most common form is X-linked sideroblastic anemia (XLSA), caused by ALAS2 mutations. The anemia occurs principally in males; however, familial and sporadic cases have been described that affect only females, possibly due to excessively skewed X-chromosome inactivation of the normal allele for the ALAS2 gene [3].
Acquired SA is more common and include two principal categories; Clonal SA and acquired types. Clonal SA which are the most common SA encountered in clinical practice are a bone marrow stem cell disorders that are currently classified within the broad group of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) and named in the updated 2016 World Health Organization (WHO) classification of hematopoietic neoplasms as; MDS with ring sideroblasts and single lineage dysplasia (MDS-RS-SLD), MDS with ring sideroblasts and multilineage dysplasia (MDS-RS-MLD) and myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) [4]. Mutations in protein constituents of the spliceosome, that mediates maturation of primary mRNA transcripts to mature mRNAs lacking introns, have been identified as being common in MDS-RS. Specifically, the acquired heterozygous missense alleles of theSF3B1 (splicing factor 3B, subunit 1) component of the splicing machinery are present in up to 85% of patients with MDS-RS-SLD, MDS-RS-MLD and MDS/MPN-RS-T [5,6].
On the other hand, non-clonal SA could be secondary to drugs, heavy metal poisoning (Lead, Arsenic), copper deficiency, alcohol use, hypothermia, or chronic neoplastic disease [7].
Herein, we report a challenging case of sideroblastic anaemia secondary to pyridoxin deficiency presented as pregnancy associated severe, recurrent anaemia.