Iron Refractory Iron Deficiency Anemia.pptx

Iridia information and guidelines presented in simple format

1. Iron Refractory Iron Deficiency Anaemia Guide & Moderator-Dr. Sonali Mohapatra Presenter- Dr.Karthika IK

2. OUTLINE

3. Background

4. Why iron is gold..?

5. Definition of anemia- who

6. DEFINITIONS

7. Definitions contd

8. Quick review on iron metabolism

9. Hepcidin overview

10. Iron regulation and Hepcidin

11. Interesting facts on hepcidin The amphipathic structure of hepcidin and its extensive disulfide bonding are common characteristics of antimicrobial and antifungal peptides. Patients with hereditary hemochromatosis, a disease generally resulting from relative hepcidin deficiency, are reported to develop infections caused by unusual microorganisms ( Vibrio , Yersinia and Listeria ), But this susceptibility could be related to the bacteria benefitting from increased iron levels rather than from the loss of any direct antibacterial effect of hepcidin.

12. HEREDITARY CONDITIONS – IRON RELATED ANEMIAS Hereditary conditions in which dietary iron intake is adequate but there is a block related to proper absorption of iron or its redistribution from stores Rare inherited Iron–related anemias Gene affected Defects of iron transport/uptake Hypotransferrinemia DMT1 mutations Defect of iron absorption IRIDA- TMPRSS Defects of iron recycling Aceruloplasminemia Defects of erythroid mitochondrial iron utilization X-linked sideroblastic anaemia AR sideroblastic anaemia

13. IRIDA-History

14. The TMPRSS6 gene encodes matriptase-2, a serine protease that represses hepcidin expression by cleaving membrane-bound hemojuvelin

15. TMPRSS6 gene and protocol for making genetic diagnosis in IRIDA The TMPRSS6 gene is located on chromosome 22 Encodes for a transmembrane type II serine protease that suppresses hepcidin secretion by cleaving hemojuvilin , a surface co-receptor in BMP-6-SMAD signaling pathway. The gene has 18 exons and encodes an 802 amino acid protein that has 4 domains Mutations like missense, frameshift, splicing etc in the serine protease domain are likely to affect the protein function most severely. Considering the heterogeneous nature of mutations it is imperative to screen and sequence all 18 exons The mutation needs to involve both alleles either as a homozygous mutation or a compound heterozygous mutation to qualify for a confirmed diagnosis of IRIDA since it is an autosomal recessive disorder .

16. IRIDA- definition

17. When to suspect IRIDA

18. ALGORITHM

19. HURDLES IN DIAGNOSING IRIDA Despite above suspicion, there is quiet a bit of overlap with other differential causes which may lead to oral iron refractoriness and it is advised to stringently look for and treat these acquired GI disorders . IRIDA is an orphan condition and sequencing for the whole TMPRSS6 gene is cumbersome and difficult. D etailed history on compliance with oral iron therapy since in our population it is very likely that parents might shift to an irregular daily iron schedule or completely stop oral iron when child complains of mild side effects. If there is such a suspicion related to compliance or if there is evidence of side effects experienced by the child, it is better to change formulation of iron and go in for a repeat assessment 3–4 weeks later.

20. Treatment of IRIDA

21. Future treatment

22. Take home message

23. De Falco L, Sanchez M, Silvestri L, et al. Iron refractory iron deficiency anemia . Haematologica . 2013;98(6):845-853. doi:10.3324/haematol.2012.075515 A structured approach to iron refractory iron deficiency anemia (IRIDA) diagnosis (SAID): The more is “SAID” about iron, the less ,Prateek Bhatia,Richa Jain,Aditya Singh- Pediatric Hematology Oncology Journal, Elsevier, August 2017 A review on iron-refractory iron-deficiency anemia Thangavelu Sangeetha, Varsha T, Mariappan Vignesh, Arumugam Vijaya Anand, Basavaraju Preethi Year : 2019 | Volume:  6 | Issue Number:  2 | Page: 57-61 Nelson’s textbook of Peadiatrics references

24. Thank you