ASSIGNMENT

SUBMITTED BY

Name: Muhammad Uzair Aslam

Reg. No: 2017-ag-9300

Section: D

Subject: Plant Breeding and Genetics

SUBMITTED TO

Prof. Dr. Aslam.

 ASSIGNMENT

Topic: GENETIC DISEASES IN HUMANS

Hemochromatosis (Iron Overload)

Introduction

Hereditary hemochromatosis is an inherited (genetic) disorder in which there is excessive

accumulation of iron in the body (iron overload). It is a common genetic disorder among
Caucasians in the United States, affecting approximately 1million people in the United States.
Individuals affected with hereditary hemochromatosis may have no symptoms or signs (and have
normal longevity), or they can have severe symptoms and signs of iron overload that include sexual
dysfunction, heart failure, joint pains, cirrhosis of the liver, diabetes, fatigue, and darkening of
skin.

In individuals with hereditary hemochromatosis, the daily absorption of iron from the intestines is
greater than the amount needed to replace losses. Since the normal body cannot increase iron
excretion, the absorbed iron accumulates in the body. At this rate of iron accumulation, a man with
hemochromatosis can accumulate 20 grams of total body iron by age 40 to 50. This excess iron
deposits in the joints, liver, testicles, and heart, causing damage to these organs and signs and
symptoms of hemochromatosis. Women with hemochromatosis accumulate iron at a slower rate
than men because they lose more iron than men due to iron loss from menstruation and
breastfeeding.

Mechanism of inheritance of hemochromatosis

Hereditary hemochromatosis is an autosomal recessive disorder, which means an individual has

the possibility of developing iron overload only when a pair of abnormal genes are inherited from
both parents.

There are primarily two mutations associated with hereditary hemochromatosis; C282Y and
H63D. The numbers 282 and 63 designate the location of the defects on the HFE gene located on
chromosome number 6. An individual who inherits two C282Y mutations (one from each parent)
is called a C282Y homozygote, and has a significant chance of developing hemochromatosis. In
fact, C282Y homozygotes account for the majority of cases of hereditary hemochromatosis.
Patients who inherit one C282Y mutation from one parent and another H63D mutation from
another parent are called compound heterozygotes, accounting for a small number of the cases of
hereditary hemochromatosis.

Symptoms and Signs of hemochromatosis

People with early hemochromatosis have no symptoms and are unaware of their condition.
The disease may then be suspected when elevated iron blood levels are noted by routine
blood testing.
 In men, symptoms may not appear until 30-50 years of age. Iron deposits in the
skin cause darkening of the skin. Since females lose iron through menstrual blood
loss, non-menstruating women develop symptoms 15 to 20 years later.
 Iron deposits in the pituitary gland and testicles cause shrinkage of the testicles and
impotence.
 Iron deposits in the pancreas cause a decrease in insulin production resulting in
diabetes.
 Iron deposits in the heart muscle can cause cardiomyopathy and lead to heart failure
as well as abnormal heart rhythms.
 Iron accumulation in the liver causes scarring of the liver (cirrhosis) and an
increased risk of developing liver cancer.

Diagnostics of hemochromatosis

Most patients with hemochromatosis are diagnosed between the ages of 30 and 50; and about 75%
have no symptoms. Hemochromatosis is discovered when elevated levels of iron in the blood are
found as part of routine blood testing; or when blood iron levels are measured as in screening
studies in family members of patients with hereditary hemochromatosis. Some patients are
diagnosed as having hemochromatosis when their doctors perform blood iron levels as part of the
evaluation for abnormal elevations in blood levels of liver enzymes, AST and ALT. However,
symptoms of skin bronzing or hyperpigmentation (about 70% eventually develop this symptom),
diabetes, liver disease, arthropathy, hypogonadism, cardiomyopathy, and impotence or no
menstrual periods (amenorrhea) may be present and may suggest that additional screening tests
such as transferrin saturation and other blood and liver tests be ordered.

Treatment

The most effective treatment for hemochromatosis is to reduce iron in the body by phlebotomy
(withdrawal of blood from the arm veins). One unit of blood, which contains 250 mg of iron,
usually is withdrawn every one to two weeks. Serum ferritin and transferrin saturation are checked
every two to three months. Once ferritin levels are below 50 ng/ml and transferrin saturations are
below 50%, the frequency of phlebotomies are reduced to every two to three months. When
hemochromatosis is diagnosed early and is treated effectively, damage to the liver, heart, testicles,
pancreas and joints can be prevented completely, and patients maintain normal health. In patients
with established cirrhosis, effective treatment can improve the function of the heart, skin color,
and diabetes. However, cirrhosis is irreversible and the risk of developing liver cancer remains.

The benefits of therapeutic phlebotomy in hemochromatosis are as follows:

 It prevents the development of liver cirrhosis and liver cancer if the disease is discovered
and treated early.
 It improves liver function partially in patients who have already developed advanced
cirrhosis.
 It improves or completely resolves symptoms of weakness, liver pain, joint pain, and
fatigue.
 It improves function of the heart in patients with mild and early heart disease.
 HARTNUP DISEASE

Introduction

Hartnup disease is a condition caused by the body's inability to absorb certain protein building
blocks (amino acids) from the diet. As a result, affected individuals are not able to use these amino
acids to produce other substances, such as vitamins and proteins. Most people with Hartnup disease
are able to get the vitamins and other substances they need with a well-balanced diet.

People with Hartnup disease have high levels of various amino acids in their urine (aminoaciduria).
For most affected individuals, this is the only sign of the condition. However, some people with
Hartnup disease have episodes during which they exhibit other signs, which can include skin
rashes; difficulty coordinating movements (cerebellar ataxia); and psychiatric symptoms, such as
depression or psychosis. These episodes are typically temporary and are often triggered by illness,
stress, nutrient-poor diet, or fever. These features tend to go away once the trigger is remedied,
although the aminoaciduria remains. In affected individuals, signs and symptoms most commonly
occur in childhood.

Hartnup disease is estimated to affect 1 in 30,000 individuals.

Causes

Hartnup disease is caused by mutations in the SLC6A19 gene. This gene provides instructions for
making a protein called B0AT1, which is primarily found embedded in the membrane of intestine
and kidney cells. The function of this protein is to transport certain amino acids into cells. In the
intestines, amino acids from food are transported into intestinal cells then released into the
bloodstream so the body can use them.

SLC6A19 gene mutations result in the production of a B0AT1 protein with reduced activity. As a
result, specific amino acids cannot be taken in by cells and are instead removed from the body as
waste. Because these amino acids are removed from the body without being used, people with this
condition may be lacking (deficient) in certain amino acids and vitamins. However, individuals
who are nutrient-deficient due to their diet, illness, stress, or a variety of other reasons, can develop
serious signs and symptoms of this condition including rashes, cerebellar ataxia, and psychiatric
symptoms.
Inheritance pattern of disease

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene
in each cell have mutations. The parents of an individual with an autosomal recessive condition
each carry one copy of the mutated gene, but they typically do not show signs and symptoms of
the condition.

Symptoms

Your brain and skin remain healthy and function properly if you get the required amount of vitamin
B complex. If you have Hartnup disease, you can’t absorb certain amino acids properly. This
impedes your body’s ability to produce protein and to make vitamin B complex. It can trigger
specific mental and physical symptoms, including:

 Skin rash
 Anxiety
 Rapid mood swings
 Delusions
 Hallucinations
 Intention tremor
 Speech difficulties
 Unsteady wide-based gait, in which you walk with your legs farther apart than normal
 Abnormalities in muscle tone, in which your muscles become tighter or lose tone
 Short stature
 Sensitivity to light
 A skin rash called “pellagra” is a common symptom.

Diagnosis

If your doctor suspects you have Hartnup disease, they may order a urinalysis test. They will collect
a sample of your urine to send to a laboratory to measure the amount of amino acids excreted
through your urine. If there are high levels of “neutral” amino acids in your urine, it may be a sign
of Hartnup disease.
Treatment

If you’re diagnosed with Hartnup disease, your doctor will likely advise you to change your diet,
avoid sunlight, and avoid sulfonamide drugs.

Dietary changes:

Since those with Hartnup disease can’t produce enough niacin, consuming foods that contain
niacin can significantly reduce your symptoms. Good sources of niacin include:

 Red meat
 Poultry
 Fish
 Peanut butter
 Fortified grains
 Whole grains
 Potatoes

Red meat, poultry, fish, and peanuts are also excellent sources of protein. Choose lean cuts of red
meat and skinless poultry. The fat and skin of meat and poultry are rich sources of saturated fat.
Eating too much saturated fat can raise your risk of high cholesterol.

Your doctor may also suggest taking vitamin B complex or niacin supplements, such as nicatonic
acid. Your doctor may also advise you to avoid direct exposure to the sun. For example, they may
encourage you to wear sunscreen and protective clothing.
 MARFAN SYNDROME

Introduction

Marfan syndrome is a heritable condition that affects the connective tissue. The primary purpose
of connective tissue is to hold the body together and provide a framework for growth and
development. In Marfan syndrome, the connective tissue is defective and does not act as it should.
Because connective tissue is found throughout the body, the syndrome can affect many body
systems, including the skeleton, eyes, heart and blood vessels, nervous system, skin, and lungs.
Marfan syndrome affects men, women, and children, and has been found among people of all races
and ethnic backgrounds.

Causes of syndrome

Marfan syndrome is caused by a defect, or mutation, in the gene that determines the structure of
fibrillin-1, a protein that is an important part of connective tissue. A person with Marfan syndrome
is born with the disorder, even though it may not be diagnosed until later in life.

The defective gene that causes Marfan syndrome can be inherited: The child of a person who has
Marfan syndrome has a 50 percent chance of inheriting the disease. Sometimes a new gene defect
occurs during the formation of sperm or egg cells, making it possible for two parents without the
disease to have a child with the disease. But this is rare. Two unaffected parents have only a 1 in
10,000 chance of having a child with Marfan syndrome. Possibly 25 percent of cases are due to a
spontaneous mutation at the time of conception.

Symptoms

Marfan syndrome affects different people in different ways. Some people have only mild
symptoms, while others are more severely affected. In most cases, the symptoms progress as the
person ages. The body systems most often affected by the syndrome are:

 Skeleton. People with the syndrome are typically very tall, slender, and loose-jointed.
Because Marfan syndrome affects the long bones of the skeleton, a person's arms, legs,
 fingers, and toes may be disproportionately long in relation to the rest of the body. A person
with the syndrome often has a long, narrow face, and the roof of the mouth may be arched,
causing the teeth to be crowded. Other skeletal problems include a sternum (breastbone)
that is either protruding or indented, curvature of the spine (scoliosis), and flat feet.
 Eyes. More than half of all people with the condition experience dislocation of one or both
lenses of the eye. The lens may be slightly higher or lower than normal, and may be shifted
off to one side. The dislocation may be minimal, or it may be pronounced and obvious.
One serious complication that may occur with this disorder is retinal detachment. Many
people with the condition are also nearsighted (myopic), and some can develop early
glaucoma (high pressure within the eye) or cataracts (the eye's lens loses its clearness).
 Heart and blood vessels (cardiovascular system). Marfan syndrome patients have
problems associated with the heart and blood vessels. Because of faulty connective tissue,
the wall of the aorta (the large artery that carries blood from the heart to the rest of the
body) may be weakened and stretch, a process called aortic dilatation. Aortic dilatation
increases the risk that the aorta will tear (aortic dissection) or rupture, causing serious heart
problems or sometimes sudden death. Sometimes, defects in heart valves can also cause
problems. In some cases, certain valves may leak, creating a "heart murmur," which a
doctor can hear with a stethoscope. Small leaks may not result in any symptoms, but larger
ones may cause shortness of breath, fatigue, and palpitations (a very fast or irregular heart
rate).
 Nervous system. The brain and spinal cord are surrounded by fluid contained by a
membrane called the dura, which is composed of connective tissue. Marfan syndrome
patients grow older, the dura often weakens and stretches, then begins to weigh on the
vertebrae in the lower spine and wear away the bone surrounding the spinal cord. This is
called dural ectasia. These changes may cause only mild discomfort; or they may lead to
radiated pain in the abdomen; or to pain, numbness, or weakness in the legs.
 Skin. Many people with Marfan syndrome develop stretch marks on their skin, even
without any weight change. These stretch marks can occur at any age and pose no health
risk. However, people with Marfan syndrome are also at increased risk for developing an
abdominal or inguinal hernia, in which a bulge develops that contains part of the intestines.
  Lungs. Although connective tissue problems make the tiny air sacs within the lungs less
elastic, people with Marfan syndrome generally do not experience noticeable problems
with their lungs. If, however, these tiny air sacs become stretched or swollen, the risk of
lung collapse may increase. Rarely, people with Marfan syndrome may have sleep-related
breathing disorders such as snoring, or sleep apnea (which is characterized by brief periods
when breathing stops).

Diagnosis

There is no specific laboratory test, such as a blood test or skin biopsy, to diagnose Marfan
syndrome. The doctor and/or geneticist (a doctor with special knowledge about inherited diseases)
relies on observation and a complete medical history, including:

 Information about any family members who may have the disorder or who had an early,
unexplained, heart-related death.
 A thorough physical examination, including an evaluation of the skeletal frame for the ratio
of arm/leg size to trunk size.
 An eye examination, including a "slit lamp" evaluation.
 Heart tests such as an echocardiogram (a test that uses ultrasound waves to examine the
heart and aorta).

Treatment

Because a number of body systems may be affected, a person with Marfan syndrome should be
cared for by several different types of doctors. A general practitioner or pediatrician may oversee
routine health care and refer the patient to specialists such as a cardiologist (a doctor who
specializes in heart disorders), an orthopaedist (a doctor who specializes in bones), or an
ophthalmologist (a doctor who specializes in eye disorders), as needed. Some people with Marfan
syndrome also go to a geneticist.
 CYSTIC FIBROSIS

Introduction

Cystic fibrosis is an inherited disorder that causes severe damage to the lungs, digestive system
and other organs in the body. Cystic fibrosis affects the cells that produce mucus, sweat and
digestive juices. These secreted fluids are normally thin and slippery. But in people with cystic
fibrosis, a defective gene causes the secretions to become sticky and thick. Instead of acting as a
lubricant, the secretions plug up tubes, ducts and passageways, especially in the lungs and
pancreas.

Causes

In cystic fibrosis, a defect (mutation) in a gene changes a protein that regulates the movement of
salt in and out of cells. The result is thick, sticky mucus in the respiratory, digestive and
reproductive systems, as well as increased salt in sweat.

Many different defects can occur in the gene. The type of gene mutation is associated with the
severity of the condition.

Children need to inherit one copy of the gene from each parent in order to have the disease. If
children inherit only one copy, they won't develop cystic fibrosis. However, they will be carriers
and possibly pass the gene to their own children.

Symptoms

Cystic fibrosis signs and symptoms vary, depending on the severity of the disease. Even in the
same person, symptoms may worsen or improve as time passes. Some people may not experience
symptoms until adolescence or adulthood.

Respiratory signs and symptoms:

 A persistent cough that produces thick mucus (sputum)

 Wheezing
 Breathlessness
 Exercise intolerance
  Repeated lung infections
 Inflamed nasal passages or a stuffy nose

Digestive signs and symptoms:

 Foul-smelling, greasy stools

 Poor weight gain and growth
 Intestinal blockage, particularly in newborns (meconium ileus)
 Severe constipation

Risk Factor

 Family history. Because cystic fibrosis is an inherited disorder, it runs in families.

 Race. Although cystic fibrosis occurs in all races, it is most common in white people of
Northern European ancestry.

Prevention

If you or your partner has close relatives with cystic fibrosis, you both may want to undergo genetic
testing before having children. The test, which is performed in a lab on a sample of blood, can help
determine your risk of having a child with cystic fibrosis.

If you're already pregnant and the genetic test shows that your baby may be at risk of cystic fibrosis,
your doctor can conduct additional tests on your developing child.

Genetic testing isn't for everyone. Before you decide to be tested, you should talk to a genetic
counselor about the psychological impact the test results might carry.
 NOONAN SYNDROME

Introduction

Noonan syndrome is a disorder that involves unusual facial characteristics, short stature, heart
defects present at birth, bleeding problems, developmental delays, and malformations of the bones
of the rib cage.

Noonan syndrome is caused by changes in one of several autosomal dominant genes. A person
who has Noonan syndrome may have inherited an altered (mutated) gene from one of his or her
parents, or the gene change may be a new change due to an error carried by the egg or sperm or
occurring at conception. Alterations in four genes - PTPN11, SOS1, RAF1 and KRAS - have been
identified to date.

Noonan syndrome is present in about 1 in 1,000 to 1 in 2,500 people.

Symptoms of Noonan Syndrome

Symptoms of Noonan syndrome may include the following:

 A characteristic facial appearance.

 Short stature.
 Heart defect present at birth (congenital heart defect).
 A broad or webbed neck.
 Minor eye problems such as strabismus in up to 95 percent of individuals.
 Bleeding problems such as a history of abnormal bleeding or bruising.
 An unusual chest shape with widely-spaced and low set nipples.
 Developmental delay of varying degrees, but usually mild.
 In males, undescended testes (cryptorchidism).

Inheritance Pattern

Noonan syndrome is inherited in families in an autosomal dominant pattern. This means that a
person who has Noonan syndrome has one copy of an altered gene that causes the disorder. In
about one-third to two-thirds of families one of the parents also has Noonan syndrome. The parent
who has Noonan syndrome has a 1 in 2 (50 percent) chance to pass on the altered gene to a child
who will be affected; and a 1 in 2 (50 percent) chance to pass on the normal version of the gene to
a child who will not have Noonan syndrome. In many individuals who have Noonan syndrome,
the altered gene happens for the first time in them, and neither of the parents has Noonan syndrome.
This is called a de novo mutation. The chance for these parents to have another child with Noonan
syndrome is very small (less than 1 percent).

Diagnosis

Individuals who have Noonan syndrome have normal chromosome studies. Four genes - PTPN11,
SOS1, RADF1 and KRAS - are the only genes that are known to be associated with Noonan
syndrome. Approximately 50 percent of individuals with Noonan syndrome have mutations in the
PTPN11 gene. Twenty percent of those with Noonan Syndrome have mutations in the SOS1.
Mutations in the RAF1 gene account for between 10 and 15 percent of Noonan syndrome cases.
About 5 percent of people with Noonan syndrome have mutations in the KRAS gene and usually
have a more severe or atypical form of the disorder.

Treatment

Treatment for individuals who have Noonan syndrome is based on their particular symptoms.
Heart problems are treated in the same way as they are for individuals in the general population.
Early intervention programs are used to help with developmental disabilities, when present.
Bleeding problems that can be present in Noonan syndrome may have a variety of causes and are
treated according to their cause. Growth problems may be caused by lack of growth hormone and
may be treated with growth hormone treatment. Symptoms such as heart problems are followed
on a regular basis.