This document discusses refractory anemia and iron-refractory iron-deficiency anemia (IRIDA). It provides details on: 1. A case of a 5-year-old female child diagnosed with iron deficiency anemia since age 1 who shows ringed sideroblasts on bone marrow staining, indicating a diagnosis of congenital sideroblastic anemia. 2. IRIDA is a rare disorder characterized by defects in both iron absorption and utilization, causing iron-deficiency anemia that is refractory to oral iron and only partially responsive to parenteral iron. It is caused by mutations in the TMPRSS6 gene which dysregulates hepcidin production. 3.

1. Refractory anemia
Allwyn rayalu

2. ANEMIA
• Anemia is defined as a reduction of the
hemoglobin concentration or red blood cell
(RBC) volume below the range of values
occurring in healthy persons. “Normal”
hemoglobin and hematocrit (packed red cell
volume) vary substantially with age and sex

4. • 5 year female child with pallor since one year
of age
• No worms, active bleeding, diarrhea
• Hospitalized for past for LRTI for 3- 4 times
• Diagnosed IDA in the past and needed
transfusion
• Born of a consanguineous marriage with no
blood transfusions in the past
• O/E – Wt - 13kg , Ht – 107cm, pallor ++
• Liver 1 cm, spleen – 3 cm
• No icterus, petichiae, SE - Normal

5. • Inv.: Hb 6.5 gm%, WBC 6500, N40, L56, E4
MCV 59, MCH 20, MCHC 30, RDW 21;
Platelets 2.5 lacs, RBC 2.3 million
• PS: Micro+++, Hypo+++, Aniso++, Ovalo+
• SI 125, TIBC 350, TS 50%, Ferritin 250 ng/ml
• MT -ve, Xray chest normal,
• Hb Electrophoresis: Normal

6. • Bone marrow – cellularity was normal,
erythroid hyperplasia, megakaryocytes normal
• Iron staining of bone marrow shows ringed
sideroblast
• Congenital sideroblastic anemia

12. • INFANTILE POIKILOCYTOSIS AND HEREDITARY
PYROPOIKILOCYTOSIS
• COPPER DEFICIENCY
• DEFECTS OF IRON METABOLISM

13. Iron-Refractory Iron-Deficiency
Anemia
• IRIDA is a rare, autosomal recessive disorder
of systemic iron balance characterized by
defects in both the absorption and the
utilization of iron. Patients with IRIDA exhibit
iron-deficiency anemia that is refractory to
oral iron therapy and only partially responsive
to parenteral iron administration

14. • IRIDA is caused by loss-of-function mutations
in the gene TMPRSS6 (transmembrane serine
protease 6)
• IRIDA results in dysregulated production of
hepcidin
• Hepcidin is abnormally high

15. Pathophysiology
• the development of systemic iron deficiency in
response to impaired intestinal absorption,
• the inefficacy of oral iron formulations in
treating the anemia,
• the impaired utilization of parenteral iron
formulations, which require macrophage
processing before the iron can be made
available for erythropoiesis

16. • Patients with IRIDA demonstrate a
hypochromic, microcytic anemia associated
with severe hypoferremia that usually
presents in early childhood
• Hypoferremia is severe, with transferrin
saturation typically less than 5 %
• Sequencing of the TMPRSS6 gene may be
performed to establish the genetic diagnosis

17. • RA defined as part of the heterogeneous
group of Myelodysplasticsyndrome that affects
the production normal red blood cells from
thebone marrow.
• Anemia is refractory - Non responsiveness to
all conventional formsof therapy

18. MDS
• Clonal hematopoietic stem cell disorders
characterized bycytopenias, dysplasia in one
or more of the major myeloidcell lines,
ineffective hematopoiesis with cellular
marrowand risk for leukemic transformation.

19. PREDISPOSING FACTORS
HEREDITARY
1. Down's syndrome
2. NF
3.Congenital Neutropenia
4,Fanconi's anemia
5.Shwachman Diamond syndrome
6.Diamond Blackfan syndrome

20. PREDISPOSING FACTORS
• Acquired
1. Radiation
2.Mutation
3.Alkylating agents
4.Tabacoo
5.Benzene
6. Aplastic anemia

23. Evaluvation of MDS
1. History :• Prior exposure to chemotherapy/ radiation•
Recurrent infections, Bleeding
2. Examination• Pallor/ Splenomegaly
3. Blood counts:• Hb,TLC,Platelet count, Reticulocyte
count
4. Peripheral smear:• Macrocytosis, Cytopenias, Pseudo -
Pelger Huet anomaly, Hypogranular Neutrophils
5. BM aspirate / Biopsy
6. Exclusion of reactive causes• Megaloblastic anemia,
HIV infection, Alcoholism

24. Clinical presentation
1. Anemia
2. Lethargy
3. Weakness
4.Fainting
5. Palpitation
6. Dizziness
7. Headache
8. Menstrual abnormalities
9. Poor appetite
10.Irritability

25. REFRACTORY CYTOPENIA WITH
UNILINEAGEDYSPLASIA
• Dysplasia > 10% in one cell lineage
• Blasts < 5% of marrow nucleated cells
• 10 to 20% of all cases of MDS
• 65 - 70 years
• M: F equal predilection
• C/F due to cytopenias

26. Refractory anemia
• It includes del 20q,
• Abnormality of 5 /7
Peripheral smear:
• Normocytic, Normochromic or Macrocytic picture
• AnisiopoikilocytosisDysplasia - limited to
erythroid lineage
• Myeloid & Megakaryocytic lineage normal
Bone marrow: Hypercellular, Myeloblast < 5%

27. Childhood MDS
• Rare ( < 5%)
• Aggressive clinical course
• Transform to AML in short period
• Respond to therapy is poor
• Survival 9-10 months
• 60 - 70 % have cytogenetic abnormalities
Associated with:• Kostmann's syndrome• Diamond
Blackfan anemia• Fanconi's anemia• Down's
syndrome• Neurofibromatosis 1

28. • Thank you