The document discusses a case study of a 39-year-old male patient with hereditary hemochromatosis who was found to be homozygous for the HFE C282Y mutation. It provides background on the role of the HFE and HJV proteins in regulating hepcidin production and iron absorption. Whole exome sequencing identified an additional novel HJV mutation, Asp355Tyr, in this patient. The document also briefly summarizes whole exome sequencing results from 50 patients at the hospital, and mentions recent Nobel Prize-winning work on modified mRNA vaccines and possibilities for future tolerogenic vaccines.

1. The double helix and the liver
Prof. A. Koshy, MD
VPS Lakeshore hospital
Cochin, India.
Nov 2023

2. Case 25
SAR 39 y M, Jun 2009, ALT from 2004
Fe Sat 83%, Ferritin 3540 ng/mL
L Bx (2009): Grade 4 iron
WES: homozygous HFE C282Y (2nd report from
India)
134534
years
10
12
14
16
18
20
0
1000
2000
3000
4000
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
Ferritin
Hemoglobin
Phlebotomy
Koshy A et al. J Clin Exp Hepatol 2020;10:163

3. HFE & HJV
HFE, HJV cell membrane complex
Activation of Hepcidin promoter (HAMP)
Hepcidin inhibits iron absorption
Pantopoulos K. Front Nutr. 2018;5:103.

4. HJV Asp355Tyr
RaptorX HJV
Koshy A et al. J Clin Exp Hepatol 2020;10:163
Wild type Asp355Tyr

5. Lakeshore data
• Whole exome sequencing 50
• Pathogenic 11
• Likely pathogenic 30
• Unexplained 9

6. Base-modified mRNA vaccine
APC / Dendrtic cell
↑ Protein
https://www.nobelprize.org/prizes/medicine/2023/press-release/

7. Future: Tolerogenic vaccine
Wardell CM et al. Nature Biotech 2021;31:419