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.