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Hemochromatosis

Outline
Introduction
Normal Iron Absorption
Pathophysiology
Signs and Symptoms
Lab Work-up
Treatment
Journal

Introduction
Hemochromatosis

is a disorder in

iron metabolism
Increase total body iron: from 2.5g
15g
Excess iron absorption, saturation of
iron binding proteins and deposition
of hemosiderin in tissues
Free iron is toxic because of its
ability to form free radicals.

Mostly

affects liver, pancreas and


the skin.
Bronze Diabetes
Autosomal recessive disorder
(Genetic)
Common in Europe particularly in
Ireland and Scotland

Hereditary/ Primary Hemochromatosis


Type 1

Type 2A

Type 2B

Type 3

Type 4

HFE Mutation

Hepcidin
Mutation

Hemojuveli
n Mutation

Transferrin
receptor 2
Mutation

Ferroportin
Mutation

Primary
Hemochromato
sis

Juvenile
Hemochromatosis

Normal Iron metabolism:


Intestinal Absorption

Normal Iron metabolism:


Intestinal Absorption

Ferrireductase
Converts ferric to ferrous form

DMT1
Transport ferrous into the lumen of enterocytes

Ferritin
Storage form of Iron

Ferroportin
transport Ferritin out of the cell

Hephaestin
Converts ferrous to Ferric form

Distribution of Iron in 70kg


adult male
Transferrin
Hemoglobin
Ferritin
Absorption
Losses

3-4mg
2500mg
1000mg
1mg/d
1mg/d

Cellular Uptake of Iron

Normal Iron metabolism:


Macrophage Recycling

Hepcidin: Main
Regulator

Hepcidin Regulation

Pathophysiology
Mutations

in the HFE Gene:

C282Y Mutation: The cysteinyl residue at

position 282 is replaced by tyrosyl residue.


Most frequent

H63D Mutation: The histidyl residue at

position 63 is replaced by aspartyl residue.


S65C Mutation: Less frequent
C282Y/H63D compound heterozygous
group

Inhibition

of complex formation
decreased surface expression of HFE
Low circulating levels of hepcidin
increases ferroportin expression
Increased intestinal iron absorption
Accumulation of excessive iron
Ferritin is increased increased
hemosiderin production

Summary of Events

Signs and Symptoms


Joint

pain
Diabetes
Loss of libido
Impotence
Heart failure
Bronze pigmentation of the skin

Lab Work-up
Normal

values:

Transferrin Saturation with iron

82% (16 to 35 %)
Serum Ferritin

3200ug/L (29 to 248ug/L Males)

Treatment
Diet

modification
Phlebotomy
Chelation Therapy (deferoxamine)

Journal

Relevance of dietary iron


intake and bioavailability in
the management of HFE
hemochromatosis: a
systematic review
Diego Mororetti, Gerrigje M van Doorn, Dorine W Swinkels,
and Alida Melse-Boonstra

Introduction
Hereditary

hemochromatosis (HH)

Heterogeneous group of disorders that is

characterized by excessive iron


bioavailability and disposition in the
body
Leads to iron loading because of a
disturbance in the negative-feedback
mechanism between dietary iron
absorption and iron status
- Dietary iron intake and bioavailability are
determinants of iron status

METHODS

Literature
search

Analyzed
qualitatively
and
Summarized
into tables

Calculation of
iron absorption
and iron
balance in HH

Results
Iron

absorption studies in HH
patients

Longitudinal

studies

Cross-sectional

studies that
investigated associations

Discussion
Studies

that have measured iron absorption in


HH subjects indicated that the iron
bioavailability in clinical penetrant HH is:
1) generally 2-10 folds higher than in wild type
individuals depending on the standardized
iron status at which groups were compared ;
2) high for iron stores, particularly for heme iron
3) Is influenced by food matrix
And therefore, is similar to iron absorption in non
HH iron deficient subjects

Despite

the suggestive evidences,


limited direct evidences was shown
to support the hypothesis that
dietary modulation can influence iron
accumulation in HH patients in a
clinically relevant manner.

In

conclusion, dietary modification


may provide an auxiliary measure to
inhibit iron accumulation and reduce
the number of required phlebotomies
in clinically confirmed HH patients.
This result could increase the
patients active involvement in
treatment and, as such, may be
beneficial for prospective disease
outcomes.