Haemochromatosis maryam asghar

GENETICS REPORT

HAEMOCHROMATOSIS

SUBMITTED TO : DR. HAMMAD AFZAL KAYANI

SUBMITTED BY : MARYAM ASGHAR (1448116)

SUBMITTED ON: JANUARY 10TH, 2017

GENETICS REPORT

Table of Contents1 IRON........................................................................................................................................4

1.1 IMPORTANCE OF IRON................................................................................................4

2 HAEMOCHROMATOSIS.......................................................................................................5

2.1 INTRODUCTION............................................................................................................5

2.2 GENETICS.......................................................................................................................6

2.3 SIGNS AND SYMPTOMS..............................................................................................8

2.4 DIAGNOSIS.....................................................................................................................8

2.5 TREATMENT................................................................................................................11

3 REFERENCES.......................................................................................................................12

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TABLE OF FIGURES

Figure 1- Iron usage in Human Body – Page 4

Figure 2 – Iron deposits in Liver – Page 5

Figure 3 – Onset of Haemochromatosis – Page 6

Figure 4 – C282Y Mutation – Page 7

Figure 5 – H63D Mutation – Page 7

Figure 6 – Types of Haemochromatosis – Page 8

Figure 7 – Signs and Symptoms – Page 8

Figure 8 – Checklist for Diagnosis – Page 10

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1 IRON Iron is a important component of our body without which we cannot live. It is known as

“Haem”. This Haem when combines with the globulin proteins form “Hemoglobin” and the iron group is present in the center of these polypeptide chains. It is necessary for firstly combining with Oxygen so that it can be transported throughout the body

1.1 IMPORTANCE OF IRON Iron in our body is used by almost all the major organs of the body especially the

Gastrointestinal Tract System where some of the Iron is broken away from Hemoglobin and is reused in next Erythrocytes made after 120 days.

Figure 1- Iron usage in Human body

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2 HAEMOCHROMATOSIS

2.1 INTRODUCTIONHaemochromatosis is a Genetic disorder that causes your body to absorb dangerous amounts

of Iron inside it. It is also more commonly known as the “Iron Overload Disorder”. The Human Body till a limit can excrete iron out from the body but increased iron absorption leads to more accumulation in various parts of the body than excretion.

The excess iron absorbed by the body is stored in various tissues and organs of the body such as under the dermis layer in the Skin, Heart, Thyroid Gland, and Pancreas. But according to statistics of the reported cases Liver is the organ most damaged because of this disease.

Figure 2- Iron deposits in Liver

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It is a slow developing disease which remains mostly asymptomatic until the organ or tissue is severely damaged. Eventually it leads to organ failure (or liver cirrhosis in terms of liver damage). When a major organ is not functioning properly in your body it eventually leads to death of the person.

Figure 3-Onset of the Haemochromatosis

2.2 GENETICSHFE gene was first discovered by a team of scientists in California in 1996. The scientists

discovered that HFE gene was located on Chromosome 6 and there are two common mutations on this gene one was C282Y and H63D that caused most of this disease.

In the mutation C282Y, The amino acid Cysteine is substituted with Tyrosine at the position 282. While in genetic mutation in H63D amino acid Histidine is substituted with amino acid Aspartate at position 63.

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Figure 4- C282Y Mutation

Figure 5 - H63D Mutation

There are four types of Haemochromatosis and depending on the type of mutation this disease can be Recessive Gene Disorder which means that an offspring should have both the copies of the faulty genes coming from both parents. The disease can also be Autosomal Dominant Gene Disorder which means that only one faulty gene copy is required from any one parent.

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Figure 6 - Types of Haemochromatosis

2.3 SIGNS AND SYMPTOMSAs Iron is absorbed in various organs of the body it shows diverged symptoms.

Figure 7 - Signs and Symptoms

2.4 DIAGNOSISTo diagnose Haemochromatosis a checklist is referred to. This checklist provides different

test at each level so that at the end you can confirm Haemochromatosis and then detect its development.

1) Blood Tests

TYPE 1

Dangerous increase in Iron absorption from Gastrointestinal Mucosa

TYPE 2

Also known as Juvenile HaemochromatosisStarts within first three decades of life

TYPE 3

Defect in TFR 2 geneIncreased Intestinal absorption

TYPE 4

Autosomal Dominant/Hereditary Hemochromatosis

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The first step in testing for Haemochromatosis is the blood test. There are two types of blood test asked by the doctor for a patient.

a. Serum Transferrin Saturation Transferrin is a protein that binds itself to the iron in the body (Transferrin Saturation). This test measures the amount of free iron and Transferrin bound iron in the blood.Normal LevelsMales = 10-50%Females = 10-45%

b. Serum Ferritin Saturation Measures the amount of iron stored in the body.Normal RangesMales = 20-300 ug/LFemales = 10-200 ug/L

2) Genetic TestingThe mutations are seen on Chromosome number 6 to identify which type of mutation took place and hence which type of Haemochromatosis is present.ResultsNo mutation= no diseaseHeterozygous = One faulty gene (Carrier) Homozygous = both faulty genes present. Disease is positive

3) Liver BiopsyA small piece of liver is removed and analyzed for any increased iron absorption.

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Figure 8 - Checklist for Diagnosis

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2.5 TREATMENTCurrently no cure is available for Haemochromatosis but with different treatments the

amount of iron in your body can be reduced. The treatments available are:

1) Phlebotomy/ VenesectionIt is the removal of 500 ml of blood from your body. There are two types of Venesection:

a. Induction: Blood is removed weekly until a year or until the iron levels come to normal levels.

b. Maintenance: It is a life- long procedure where blood is removed every 2-3 months.

2) Chelation TherapyA series of medicines are prescribed to lower the iron concentration in the blood. These medications are taken once daily.

3) DietIf a person has Haemochromatosis he/she needs to follow a set of diet which includes:

a. A healthy and balanced diet with not many iron containing foodsb. Avoid fortified iron products for example cerealsc. Avoid Iron and Vitamin C supplementsd. No alcohol as it further damages liver.

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3 REFERENCES

http:// www.mayoclinic.org/diseases-conditions/hemochromatosis/symptoms-causes/dxc- 20167290

https://www.ncbi.nlm.nih.gov/gtr/conditions/C0392514 /

https://www.ncbi.nlm.nih.gov/gtr/conditions/C1865614 /

https://www.ncbi.nlm.nih.gov/gtr/conditions/C1858664 /

https://www.ncbi.nlm.nih.gov/gtr/conditions/C1853733 /

http :// haemochromatosis.org.au/wordpress/wpcontent/uploads/2014/12/ IS1_Gentotypes_20141105_2.pdf

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