HEMOCHROMATOSIS UPDATE May 24, 2015 Paul C Adams
• To develop an approach to the diagnosis and
management of hemochromatosis
• To discuss several cases with arthropathy and
hemochromatosis
• To consider the differential diagnosis of an elevated
serum ferritin
2
Learning Objectives
• Research Grant – Gilead – Liver Fibrosis
• Advisor – LaJolla Pharmaceuticals - Hepcidin
Disclosures
19 year old man presents with sore knees, no sports injuries,
found to have Transferrin saturation 100 %, Serum ferritin 78,
C282Y homozygote
Fasting does not improve TS in the
detection of C282Y homozygotes
Blood
test
n Sensitivity
(%)
Specificity
(%)
PPV
(%)
Fasting
TS
31,796 77
(65-86)
93
(92 – 93)
2.3
(2 – 3)
Random
TS
64,230 75
(67-81)
95
(95-96)
3.5
(3 – 4)
Adams PC et al, Am J Med 2007
Adams, P. C. et al. N Engl J Med 2005;352:1769-1778
Serum Ferritin Levels in Men and Women According to Genotype
Proportion of Caucasians with an elevated serum ferritin that have the C282Y genotype
N = 44,625 Adams PC et al, Can J Gastro 2013
Chasing the ferritin
Ferritin 300-1000
NAFLD
EtOH
Uncertain
4% Misc
7% Hep C
2% Secondary
Fe Overload
HH
13%
20% 17%
33%
Wong K, Adams PC, Can J Gastro 2006
n = 363
Chasing the ferritin
Ferritin > 1000
HH
EtOH
NAFLD
Uncertain
3% Hep C 1% Misc9%
Secondary Fe
Overload
9%
11%
20%
42%
Wong K, Adams PC, Can J Gastro 2006
n = 119
MRI in the assessment of liver iron in hemochromatosis
Fifty shades of gray
29 year old C282Y homozygote scanned serially during phlebotomy
T1 map
Iron load ~ 15 g - 5.5 g Fe - 12.5 g Fe
Liver iron = 437 umol/g
Effect of iron depletion on liver fibrosis C282Y homozygote – 46 year old man
Serum ferritin = 3,833 Serum ferritin = 157, 3 years later
Hepcidin – met50del, Ceruloplasmin, Hephaestin, DMT1, Beta-2 microglobulin
HFE – C282Y, H63D, S65C, Ferroportin – 144, 162, 248 , TFR2 – 60, 172, 250
Acknowledgments
Leslie Valberg, Peter Flanagan
Mark Speechley, Ann Kertesz
Subrata Chakrabarti, Helen Harrison
Lawrie Powell, June Halliday
Mark Bassett, Gary Jeffrey
Greg Anderson, Grant Ramm
Yves Deugnier, Pierre Brissot
Romain Moirand, Dominique Guyader
Veronique David, Jean-Yves LeGall
Phyliss Sholinsky, Jim Barton, Ron Acton
Vic Gordeuk, Fitzroy Dawkins,
Emily Harris, Elizabeth Thomson
Christine and Gordon McLaren,
Dave Reboussin, John Eckfeldt, NHLBI