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.