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MENDELIAN DISORDERS :
INTRODUCTION
Mendelian disorder is a category of Genetic disorder. They are mainly
determined by alteration or mutation in the single gene .These disorders are transmitted
to the offspring on the same lines as in the principle of inheritance.The pattern of
inheritance of such mendelian disorders can be traced in a family by pedigree
analysis.most common and prevalent mendelian disorders are Haemophilia, Cystic
Fibrosis, Sickle-cell anemia, and Thalassemia. Such mendelian disorders may be
dominant or recessive. By pedigree analysis one can esily understand whwther the trait
is dominant or recessive. Similarly the trait may also be linked to the sex chromosome
as in case of Haemophilia.
It is evident that this X-linked recessive trait shows transmission from carrier
female to male progeny.

SICKLE CELL ANEMIA

What Is Sickle Cell Anemia?

Sickle cell anemia is the most common form of sickle cell disease (SCD). SCD
is a serious disorder in which the body makes sickle-shaped red blood cells. Sickle-
shaped means that the red blood cells are shaped like a crescent.

Normal red blood cells are disc-shaped and look like doughnuts without holes in
the center. They move easily through your blood vessels. Red blood cells contain an
iron-rich protein called hemoglobin. This protein carries oxygen from the lungs to the
rest of the body.Sickle cells contain abnormal hemoglobin called sickle hemoglobin or
hemoglobin S. Sickle hemoglobin causes the cells to develop a sickle, or crescent,
shape.

Sickle cells are stiff and sticky. They tend to block blood flow in the blood
vessels of the limbs and organs. Blocked blood flow can cause pain and organ damage.
It can also raise the risk for infection.

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 Normal Red Blood Cells and Sickle Cells

Figure A shows normal red blood cells flowing freely in a blood vessel. The
inset image shows a cross-section of a normal red blood cell with normal
hemoglobin. Figure B shows abnormal, sickled red blood cells blocking blood flow
in a blood vessel. The inset image shows a cross-section of a sickle cell with
abnormal (sickle) hemoglobin forming abnormal strands.

Overview
Sickle cell anemia is one type of anemia. Anemia is a condition in which your
blood has a lower than normal number of red blood cells. This condition also can occur
if your red blood cells don't contain enough hemoglobin.

Red blood cells are made in the spongy marrow inside the larger bones of the
body. Bone marrow is always making new red blood cells to replace old ones. Normal
red blood cells live about 120 days in the bloodstream and then die. They carry oxygen
and remove carbon dioxide (a waste product) from your body.

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 In sickle cell anemia, the abnormal sickle cells usually die after only about 10 to
20 days. The bone marrow can't make new red blood cells fast enough to replace the
dying ones.

Sickle cell anemia is an inherited, lifelong disease. People who have the disease
are born with it. They inherit two genes for sickle hemoglobinone from each parent.

People who inherit a sickle hemoglobin gene from one parent and a normal gene
from the other parent have a condition called sickle cell trait.

Sickle cell trait is different than sickle cell anemia. People who have sickle cell
trait don't have the disease. Like people who have sickle cell anemia, people who have
sickle cell trait can pass the sickle hemoglobin gene to their children.

SICKLE CELL MUTATION

Outlook
Sickle cell anemia has no widely available cure. However, treatments to improve
the anemia and lower complications can help with the symptoms and complications of
the disease in both children and adults. Blood and marrow stem cell transplants may
offer a cure for a small number of people.

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 Over the past 100 years, doctors have learned a great deal about sickle cell
anemia. They know its causes, how it affects the body, and how to treat many of its
complications.

Sickle cell anemia varies from person to person. Some people who have the
disease have chronic (long-term) pain or fatigue (tiredness). However, with proper care
and treatment, many people who have the disease can have improved quality of life
and reasonable health much of the time.

Because of improved treatments and care, people who have sickle cell anemia
are now living into their forties or fifties, or longer.

What Causes Sickle Cell Anemia?

Sickle cell anemia is an inherited disease. People who have the disease inherit
two genes for sickle hemoglobinone from each parent.

Sickle hemoglobin causes red blood cells to develop a sickle, or crescent, shape.
Sickle cells are stiff and sticky. They tend to block blood flow in the blood vessels of
the limbs and organs. Blocked blood flow can cause pain and organ damage. It can also
raise the risk for infection.

Sickle Cell Trait

People who inherit a sickle hemoglobin gene from one parent and a normal gene
from the other parent have sickle cell trait. Their bodies make both sickle hemoglobin
and normal hemoglobin.

People who have sickle cell trait usually have few, if any, symptoms and lead
normal lives. However, some people may have medical complications.

People who have sickle cell trait can pass the sickle hemoglobin gene to their
children. The following image shows an example of an inheritance pattern for sickle
cell trait.

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Example of an Inheritance Pattern for Sickle Cell Trait

The image shows how sickle hemoglobin genes are inherited. A person inherits
two hemoglobin genesone from each parent. A normal gene will make normal
hemoglobin (A). A sickle hemoglobin gene will make abnormal hemoglobin (S).

When both parents have a normal gene and an abnormal gene, each child has a
25 percent chance of inheriting two normal genes; a 50 percent chance of inheriting
one normal gene and one abnormal

What Are the Signs and Symptoms of Sickle Cell Anemia?

The signs and symptoms of sickle cell anemia vary. Some people have mild
symptoms. Others have very severe symptoms and often are hospitalized for treatment.

Sickle cell anemia is present at birth, but many infants don't show any signs until
after 4 months of age.

The most common signs and symptoms are linked to anemia and pain. Other
signs and symptoms are linked to the disease's complications.

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Signs and Symptoms Related to Anemia

The most common symptom of anemia is fatigue (feeling tired or weak). Other
signs and symptoms of anemia include:

Shortness of breath
Dizziness
Headaches
Coldness in the hands and feet
Paler than normal skin or mucous membranes (the tissue that lines your nose,
mouth, and other organs and body cavities)
Jaundice (a yellowish color of the skin or whites of the eyes)
Signs and Symptoms Related to Pain

Sudden pain throughout the body is a common symptom of sickle cell anemia.
This pain is called a sickle cell crisis. Sickle cell crises often affect the bones, lungs,
abdomen, and joints.

How Is Sickle Cell Anemia Diagnosed?

A simple blood test, done at any time during a person's lifespan, can detect
whether he or she has sickle hemoglobin. However, early diagnosis is very important.

In the United States, all States mandate testing for sickle cell anemia as part of
their newborn screening programs. The test uses blood from the same blood samples
used for other routine newborn screening tests. The test can show whether a newborn
infant has sickle hemoglobin.Test results are sent to the doctor who ordered the test and
to the baby's primary care doctor. It's important to give the correct contact information
to the hospital. This allows the baby's doctor to get the test results as quickly as
possible.

Health providers from a newborn screening followup program may contact you
directly to make sure you're aware of the test results.If the test shows some sickle
hemoglobin, a second blood test is done to confirm the diagnosis. The second test
should be done as soon as possible and within the first few months of life.

The primary care doctor may send you to a hematologist for a second blood test.
A hematologist is a doctor who specializes in blood diseases and disorders. This doctor
also can provide treatment for sickle cell disease if needed.
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 Doctors also can diagnose sickle cell disease before birth. This is done using a
sample of amniotic fluid or tissue taken from the placenta. (Amniotic fluid is the fluid
in the sac surrounding a growing embryo. The placenta is the organ that attaches the
umbilical cord to the mother's womb.)Testing before birth can be done as early as 10
weeks into the pregnancy. This testing looks for the sickle hemoglobin gene, rather
than the abnormal hemoglobin that the gene makes.

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How Is Sickle Cell Anemia Treated?
Sickle cell anemia has no widely available cure. However, treatments can help
relieve symptoms and treat complications. The goals of treating sickle cell anemia are
to relieve pain; prevent infections, organ damage, and strokes and control
complications (if they occur).

Blood and marrow stem cell transplants may offer a cure for a small number of
people who have sickle cell anemia. Researchers continue to look for new treatments
for the disease.Infants who have been diagnosed with sickle cell anemia through
newborn screening are treated with antibiotics to prevent infections and receive needed
vaccinations. Their parents are educated about the disease and how to manage it. These
initial treatment steps have greatly improved the outcome for children who have sickle
cell anemia.

Specialists Involved
People who have sickle cell anemia need regular medical care. Some doctors and
clinics specialize in treating people who have the disease. Hematologists specialize in
treating adults and children who have blood diseases or disorders.

Treating Pain
Medicines and Fluids

Mild pain often is treated at home with over-the-counter pain medicines, heating
pads, rest, and plenty of fluids. More severe pain may need to be treated in a day clinic,
emergency room, or hospital.

The usual treatments for acute (rapid-onset) pain are fluids, medicines,
andoxygen therapy (if the oxygen level is low). Fluids help prevent dehydration, a
condition in which your body doesn't have enough fluids. Fluids are given either by
mouth or through a vein.

Hydroxyurea

Severe sickle cell anemia can be treated with a medicine called hydroxyurea.
This medicine prompts your body to make fetal hemoglobin. Fetal hemoglobin, or
hemoglobin F, is the type of hemoglobin that newborns have.In people who have sickle
cell anemia, fetal hemoglobin helps prevent red blood cells from sickling and improves
anemia.
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 Taken daily by mouth, hydroxyurea reduces how often painful sickle cell crises
and acute chest syndrome occur. Many people taking hydroxyurea also need
fewerblood transfusions and have fewer hospital visits.

Preventing Complications
Blood transfusions are commonly used to treat worsening anemia and sickle cell
complications. A sudden worsening of anemia due to an infection or enlarged spleen is
a common reason for a blood transfusion.

Some, but not all, people who have sickle cell anemia need regular blood
transfusions to prevent life-threatening problems, such as stroke, spleen problems, or
acute chest syndrome.

Having routine blood transfusions can cause side effects. Examples include
allergic reactions and a dangerous buildup of iron in the body (which must be treated).
In general, the blood supply is fairly safe from infections such as hepatitis and HIV.

Infections
Infections can be a major complication of sickle cell anemia throughout life, but
especially during childhood. Often, infections can be prevented or treated.

To prevent infections in babies and young children, treatments include:

Daily doses of antibiotics. Treatment may begin as early as 2 months of age and
continue until the child is at least 5 years old.
All routine vaccinations (including a yearly flu shot), plus the pneumococcal
vaccine.
Regular Health Care for Children
Children who have sickle cell anemia need routine health care (just like children
who don't have the disease). They need to have their growth checked regularly. They
also need to get the routine shots that all children get.

All children younger than 2 years old should see their doctors often. Children
who have sickle cell anemia may need even more checkups. After age 2, children who
have sickle cell anemia may not need to see their doctors as often, but they usually still
need checkups at least every 6 months.These visits are a time for parents to talk with
their child's doctor and ask questions about the child's care. Talk with your child's

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doctor about eye checkups and whether your child needs an ultrasound scan of the
brain.

Until age 5, daily penicillin is given to most children who have sickle cell
anemia. Doctors also give many children a vitamin called folic acid (folate) to help
boost red blood cell production.Young children who have sickle cell anemia should
have regular checkups with a hematologist (a blood specialist).

New Treatments
Research on blood and marrow stem cell transplants, gene therapy, and new
medicines for sickle cell anemia is ongoing. The hope is that these studies will provide
better treatments for the disease. Researchers also are looking for a way to predict the
severity of the disease.

Blood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant can work well for treating sickle cell
anemia. This treatment may even offer a cure for a small number of people.The stem
cells used for a transplant must come from a closely matched donor. The donor usually
is a close family member who doesn't have sickle cell anemia. This limits the number
of people who may have a donor.

The transplant process is risky and can lead to serious side effects or even death.
However, new transplant approaches may improve treatment for people who have
sickle cell anemia and involve less risk.Blood and marrow stem cell transplants usually
are used for young patients who have severe sickle cell anemia. However, the decision
to give this treatment is made on a case-by-case basis.

Researchers continue to look for sources of bone marrow stem cellsfor

example, blood from babies' umbilical cords. They also continue to look for ways to
reduce the risks of this procedure.

Gene Therapy

Gene therapy is being studied as a possible treatment for sickle cell anemia.
Researchers want to know whether a normal gene can be put into the bone marrow
stem cells of a person who has sickle cell anemia. This would cause the body to make
normal red blood cells.

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 Researchers also are studying whether they can "turn off" the sickle hemoglobin
gene or "turn on" a gene that makes red blood cells behave normally.

New Medicines

Researchers are studying several medicines for sickle cell anemia. They include:

Decitabine: Like hydroxyurea, this medicine prompts the body to make fetal
hemoglobin. Fetal hemoglobin helps prevent red blood cells from sickling and
improves anemia. Decitabine might be used instead of hydroxyurea or added to
hydroxyurea.
Adenosine A2a receptor agonists: These medicines may reduce pain-related
complications in people who have sickle cell anemia.
5-HMF: This natural compound binds to red blood cells and increases their
oxygen. This helps prevent the red blood cells from sickling.

How Can Sickle Cell Anemia Be Prevented?

You cant prevent sickle cell anemia, because its an inherited disease. If a
person is born with it, steps should be taken to reduce complications. People who are at
high risk of having a child with sickle cell anemia and are planning to have children
may want to consider genetic counseling. A counselor can explain the risk (likelihood)
of having a child who has the disease. He or she also can help explain the choices that
are available.

You can find information about genetic counseling from health departments,
neighborhood health centers, medical centers, and clinics that care for people who have
sickle cell anemia.

Living With Sickle Cell Anemia

With good health care, many people who have sickle cell anemia can live
productive lives. They also can have reasonably good health much of the time and live
longer today than in the past. Many people who have sickle cell anemia now live into
their forties or fifties, or longer.

If you have sickle cell anemia, it's important to:

Adopt or maintain a healthy lifestyle

Take steps to prevent and control complications
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 Learn ways to cope with pain.

HEMOPHILIA

What Is Hemophilia?
Hemophilia is a rare bleeding disorder in which the blood doesn't clot normally.

If you have hemophilia, you may bleed for a longer time than others after an
injury. You also may bleed inside your body (internally), especially in your knees,
ankles, and elbows. This bleeding can damage your organs and tissues and may be life
threatening.

Overview

Hemophilia usually is inherited. "Inherited means that the disorder is passed

from parents to children through genes.People born with hemophilia have little or no
clotting factor. Clotting factor is a protein needed for normal blood clotting. There are
several types of clotting factors. These proteins work with platelets to help the blood
clot.

Platelets are small blood cell fragments that form in the bone marrowa
sponge-like tissue in the bones. Platelets play a major role in blood clotting. When
blood vessels are injured, clotting factors help platelets stick together to plug cuts and
breaks on the vessels and stop bleeding.The two main types of hemophilia are A and B.

If you have hemophilia A, you're missing or have low levels of clotting factor
VIII (8). About 8 out of 10 people who have hemophilia have type A. If you have
hemophilia B, you're missing or have low levels of clotting factor IX (9).

Rarely, hemophilia can be acquired. "Acquired means you aren't born with the
disorder, but you develop it during your lifetime. This can happen if your body forms
antibodies (proteins) that attack the clotting factors in your bloodstream. The
antibodies can prevent the clotting factors from working.

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What Causes Hemophilia?
If you have inherited hemophilia, you're born with the disorder. It's caused by a
defect in one of the genes that determine how the body makes blood clotting factor
VIII or IX. These genes are located on the X chromosomes.

Chromosomes come in pairs. Females have two X chromosomes, while males

have one X and one Y chromosome. Only the X chromosome carries the genes related
to clotting factors. A male who has a faulty hemophilia gene on his X chromosome will
have hemophilia. A female must have the faulty gene on both of her X chromosomes to
have hemophilia, which is very rare. If a female has the faulty gene on only one of her

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X chromosomes, she is a "hemophilia carrier. Carriers don't have hemophilia, but they
can pass the faulty gene to their children.

Below are two examples of how the hemophilia gene is inherited.

Inheritance Pattern for Hemophilia Example 1

The image shows one example of how the hemophilia gene is inherited. In this
example, the father doesn't have hemophilia (that is, he has two normal chromosomes
X and Y). The mother is a carrier of hemophilia (that is, she has one faulty X
chromosome and one normal X chromosome).

Each daughter has a 50 percent chance of inheriting the faulty gene from her
mother and being a carrier. Each son has a 50 percent chance of inheriting the faulty
gene from his mother and having hemophilia.

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Inheritance Pattern for HemophiliaExample 2

The image shows one example of how the hemophilia gene is inherited. In this
example, the father has hemophilia (that is, his X chromosome is faulty). The mother
isn't a hemophilia carrier (that is, she has two normal X chromosomes).

Each daughter will inherit the faulty gene from her father and be a carrier.
None of the sons will inherit the faulty gene from their father; thus, none will have
hemophilia.

Females who are hemophilia carriers usually have enough clotting factors from
their one normal X chromosome to prevent serious bleeding problems. However, up
to 50 percent of carriers may have an increased risk of bleeding.

Very rarely, a girl is born with hemophilia. This can happen if her father has
hemophilia and her mother is a carrier.

Some males who have the disorder are born to mothers who aren't carriers. In
these cases, a mutation occurs in the gene as it is passed to the child.

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What Are the Signs and Symptoms of Hemophilia?
The major signs and symptoms of hemophilia are excessive bleeding and easy
bruising.

Excessive Bleeding

The extent of bleeding depends on how severe the hemophilia is.

Children who have mild hemophilia may not have signs unless they have
excessive bleeding from a dental procedure, an accident, or surgery. Bleeding can
occur on the body's surface (external bleeding) or inside the body (internal bleeding).

Signs of external bleeding may include:

Bleeding in the mouth from a cut or bite or from cutting or losing a tooth
Nosebleeds for no obvious reason
Heavy bleeding from a minor cut
Bleeding from a cut that resumes after stopping for a short time

Signs of internal bleeding may include:

Blood in the urine (from bleeding in the kidneys or bladder)

Blood in the stool (from bleeding in the intestines or stomach)
Large bruises (from bleeding into the large muscles of the body)

Bleeding in the Joints

Bleeding in the knees, elbows, or other joints is another common form of

internal bleeding in people who have hemophilia. This bleeding can occur without
obvious injury.At first, the bleeding causes tightness in the joint with no real pain or
any visible signs of bleeding. The joint then becomes swollen, hot to touch, and painful
to bend.

Swelling continues as bleeding continues. Eventually, movement in the joint is

temporarily lost. Pain can be severe. Joint bleeding that isn't treated quickly can
damage the joint.

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Bleeding in the Brain

Internal bleeding in the brain is a very serious complication of hemophilia. It can

happen after a simple bump on the head or a more serious injury. The signs and
symptoms of bleeding in the brain include:

Long-lasting, painful headaches or neck pain or stiffness

Repeated vomiting
Sleepiness or changes in behavior
Sudden weakness or clumsiness of the arms or legs or problems walking
Double vision
Convulsions or seizures

How Is Hemophilia Diagnosed?

If you appear to have a bleeding problem, your doctor will ask about your
personal and family medical histories. This will reveal whether you or your family
members, including women and girls, have bleeding problems. However, some people
who have hemophilia have no recent family history of the disease.

You or also will likely have a physical exam and blood tests to diagnose
hemophilia. Blood tests are used to find out:

How long it takes for your blood to clot

Whether your blood has low levels of any clotting factors
Whether any clotting factors are completely missing from your blood

The test results will show whether you have hemophilia, what type of
hemophilia you have, and how severe it is.

Hemophilia A and B are classified as mild, moderate, or severe, depending on

the amount of clotting factor VIII or IX in the blood.

Mild hemophilia 540 percent of normal clotting factor

Moderate hemophilia 15 percent of normal clotting factor
Severe hemophilia Less than 1 percent of normal clotting factor

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How Is Hemophilia Treated?
Treatment With Replacement Therapy

The main treatment for hemophilia is called replacement therapy. Concentrates

of clotting factor VIII (for hemophilia A) or clotting factor IX (for hemophilia B) are
slowly dripped or injected into a vein. These infusions help replace the clotting factor
that's missing or low.

Clotting factor concentrates can be made from human blood. The blood is
treated to prevent the spread of diseases, such as hepatitis. With the current methods of
screening and treating donated blood, the risk of getting an infectious disease from
human clotting factors is very small.

Complications of Replacement Therapy

Complications of replacement therapy include:

Developing antibodies (proteins) that attack the clotting factor

Developing viral infections from human clotting factors
Damage to joints, muscles, or other parts of the body resulting from delays in
treatment
Other Types of Treatment
Desmopressin

Desmopressin (DDAVP) is a man-made hormone used to treat people who have

mild hemophilia A. DDAVP isn't used to treat hemophilia B or severe hemophilia A.

DDAVP stimulates the release of stored factor VIII and von Willebrand factor; it
also increases the level of these proteins in your blood. Von Willebrand factor carries
and binds factor VIII, which can then stay in the bloodstream longer.

DDAVP usually is given by injection or as nasal spray. Because the effect of this
medicine wears off if it's used often, the medicine is given only in certain situations.
For example, you may take this medicine prior to dental work or before playing certain
sports to prevent or reduce bleeding.

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Antifibrinolytic Medicines

Antifibrinolytic medicines (including tranexamic acid and epsilon aminocaproic

acid) may be used with replacement therapy. They're usually given as a pill, and they
help keep blood clots from breaking down.

These medicines most often are used before dental work or to treat bleeding
from the mouth or nose or mild intestinal bleeding.

Gene Therapy

Researchers are trying to find ways to correct the faulty genes that cause
hemophilia. Gene therapy hasn't yet developed to the point that it's an accepted
treatment for hemophilia. However, researchers continue to test gene therapy in clinical
trial.

Treatment of a Specific Bleeding Site

Pain medicines, steroids, and physical therapy may be used to reduce pain and
swelling in an affected joint. Talk with your doctor or pharmacist about which
medicines are safe for you to take.

Ongoing Care

If you have hemophilia, you can take steps to avoid complications. For example:

Follow your treatment plan exactly as your doctor prescribes.

Have regular checkups and vaccinations as recommended.
Tell all of your health care providerssuch as your doctor, dentist, and
pharmacistthat you have hemophilia. You also may want to tell people like
your employee health nurse, gym trainer, and sports coach about your condition.
Have regular dental care. Dentists at the HTCs are experts in providing dental
care for people who have hemophilia. If you see another dentist, tell him or her
that you have hemophilia. The dentist can provide medicine that will reduce
bleeding during dental work.
Know the signs and symptoms of bleeding in joints and other parts of the body.
Know when to call your doctor or go to the emergency room. For example,
you'll need care if you have:

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 o Heavy bleeding that can't be stopped or a wound that continues to ooze
blood.
o Any signs or symptoms of bleeding in the brain. Such bleeding is life
threatening and requires emergency care.
o Limited motion, pain, or swelling of any joint.

It's a good idea to keep a record of all previous treatments. Be sure to take this
information with you to medical appointments and to the hospital or emergency room.

CYSTIC FIBROSIS

What Is Cystic Fibrosis?

Cystic fibrosis is an inherited disease of the secretory glands. Secretory glands
include glands that make mucus and sweat.

"Inherited" means the disease is passed from parents to children through genes.
People who have CF inherit two faulty genes for the diseaseone from each parent.
The parents likely don't have the disease themselves. CF mainly affects the lungs,
pancreas, liver, intestines, sinuses, and sex organs.

Overview
Mucus is a substance made by tissues that line some organs and body cavities,
such as the lungs and nose. Normally, mucus is a slippery, watery substance. It keeps
the linings of certain organs moist and prevents them from drying out or getting
infected.

If you have CF, your mucus becomes thick and sticky. It builds up in your lungs
and blocks your airways. (Airways are tubes that carry air in and out of your
lungs.)The buildup of mucus makes it easy for bacteria to grow. This leads to repeated,
serious lung infections. Over time, these infections can severely damage your lungs.

The thick, sticky mucus also can block tubes, or ducts, in your pancreas (an
organ in your abdomen). As a result, the digestive enzymes that your pancreas makes
can't reach your small intestine.

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 These enzymes help break down food. Without them, your intestines can't fully
absorb fats and proteins. This can cause vitamin deficiency and malnutrition because
nutrients pass through your body without being used. You also may have bulky stools,
intestinal gas, a swollen belly from severe constipation, and pain or discomfort.

CF also causes your sweat to become very salty. Thus, when you sweat, you lose
large amounts of salt. This can upset the balance of minerals in your blood and cause
many health problems. Examples of these problems include dehydration (a lack of
fluid in your body), increased heart rate, fatigue (tiredness), weakness, decreased blood
pressure, heat stroke, and, rarely, death.

If you or your child has CF, you're also at higher risk for diabetes or two bone-
thinning conditions called osteoporosis and osteopenia.CF also causes infertility in
men, and the disease can make it harder for women to get pregnant.

Outlook
The symptoms and severity of CF vary. If you or your child has the disease, you
may have serious lung and digestive problems. If the disease is mild, symptoms may
not show up until the teen or adult years.

The symptoms and severity of CF also vary over time. Sometimes you'll have
few symptoms. Other times, your symptoms may become more severe. As the disease
gets worse, you'll have more severe symptoms more often.

Lung function often starts to decline in early childhood in people who have CF.
Over time, damage to the lungs can cause severe breathing problems. Respiratory
failure is the most common cause of death in people who have CF.As treatments for CF
continue to improve, so does life expectancy for those who have the disease. Today,
some people who have CF are living into their forties or fifties, or longer.

Early treatment for CF can improve your quality of life and increase your
lifespan. Treatments may include nutritional and respiratory therapies, medicines,
exercise, and other treatments.Your doctor also may recommend pulmonary
rehabilitation (PR). PR is a broad program that helps improve the well-being of people
who have chronic breathing problems.

What Causes Cystic Fibrosis?

A defect in the CFTR gene causes cystic fibrosis (CF). This gene makes a
protein that controls the movement of salt and water in and out of your body's cells. In
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people who have CF, the gene makes a protein that doesn't work well. This causes
thick, sticky mucus and very salty sweat.

Research suggests that the CFTR protein also affects the body in other ways.
This may help explain other symptoms and complications of CF.More than a thousand
known defects can affect the CFTR gene. The type of defect you or your child has may
affect the severity of CF. Other genes also may play a role in the severity of the
disease.

How Is Cystic Fibrosis Inherited?

Every person inherits two CFTR genesone from each parent. Children who
inherit a faulty CFTR gene from each parent will have CF.Children who inherit one
faulty CFTR gene and one normal CFTR gene are "CF carriers." CF carriers usually
have no symptoms of CF and live normal lives. However, they can pass the faulty
CFTR gene to their children.

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 The image below shows how two parents who are both CF carriers can pass the
faulty CFTR gene to their children.

Example of an Inheritance Pattern for Cystic Fibrosis

The image shows how CFTR genes are inherited. A person inherits two copies of
the CFTR geneone from each parent. If each parent has a normal CFTR gene and a
faulty CFTR gene, each child has a 25 percent chance of inheriting two normal genes;
a 50 percent chance of inheriting one normal gene and one faulty gene; and a 25
percent chance of inheriting two faulty genes.

Who Is at Risk for Cystic Fibrosis?

Cystic fibrosis (CF) affects both males and females and people from all racial
and ethnic groups. However, the disease is most common among Caucasians of
Northern European descent.

CF also is common among Latinos and American Indians, especially the Pueblo and
Zuni. The disease is less common among African Americans and Asian Americans.

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More than 10 million Americans are carriers of a faulty CF gene. Many of them don't
know that they're CF carriers.

What Are the Signs and Symptoms of Cystic Fibrosis?

The signs and symptoms of cystic fibrosis (CF) vary from person to person and
over time. Sometimes you'll have few symptoms. Other times, your symptoms may
become more severe.

One of the first signs of CF that parents may notice is that their baby's skin tastes
salty when kissed, or the baby doesn't pass stool when first born.

Most of the other signs and symptoms of CF happen later. They're related to how
CF affects the respiratory, digestive, or reproductive systems of the body.

Cystic Fibrosis

Figure A shows the organs that cystic fibrosis can affect. Figure B shows a cross-
section of a normal airway. Figure C shows an airway with cystic fibrosis. The
widened airway is blocked by thick, sticky mucus that contains blood and bacteria.

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Respiratory system signs and symptoms

People who have CF have thick, sticky mucus that builds up in their airways.
This buildup of mucus makes it easier for bacteria to grow and cause infections.
Infections can block the airways and cause frequent coughing that brings up thick
sputum (spit) or mucus that's sometimes bloody.

CF also can cause clubbing and low bone density. Clubbing is the widening and
rounding of the tips of your fingers and toes. This sign develops late in CF because
your lungs aren't moving enough oxygen into your bloodstream.Low bone density also
tends to occur late in CF. It can lead to bone-thinning disorders called osteoporosis and
osteopenia.

How Is Cystic Fibrosis Diagnosed?

Doctors diagnose cystic fibrosis (CF) based on the results from various tests.

Newborn Screening

All States screen newborns for CF using a genetic test or a blood test. The
genetic test shows whether a newborn has faulty CFTR genes. The blood test shows
whether a newborn's pancreas is working properly.

Sweat Test

If a genetic test or blood test suggests CF, a doctor will confirm the diagnosis
using a sweat test. This test is the most useful test for diagnosing CF. A sweat test
measures the amount of salt in sweat. For this test, the doctor triggers sweating on a
small patch of skin on an arm or leg. He or she rubs the skin with a sweat-producing
chemical and then uses an electrode to provide a mild electrical current. This may
cause a tingling or warm feeling.

Sweat is collected on a pad or paper and then analyzed. The sweat test usually is
done twice. High salt levels confirm a diagnosis of CF.

How Is Cystic Fibrosis Treated?

Cystic fibrosis (CF) has no cure. However, treatments have greatly improved in
recent years. The goals of CF treatment include:

Preventing and controlling lung infections

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 Loosening and removing thick, sticky mucus from the lungs
Preventing or treating blockages in the intestines
Providing enough nutrition
Preventing dehydration (a lack of fluid in the body)

Depending on the severity of CF, you or your child may be treated in a hospital.

Treatment for Lung Problems

The main treatments for lung problems in people who have CF are chest
physical therapy (CPT), exercise, and medicines. Your doctor also may recommend
apulmonary rehabilitation (PR) program.

Chest Physical Therapy

CPT also is called chest clapping or percussion. It involves pounding your chest
and back over and over with your hands or a device to loosen the mucus from your
lungs so that you can cough it up.

Exercise

Aerobic exercise that makes you breathe harder can help loosen the mucus in
your airways so you can cough it up. Exercise also helps improve your overall physical
condition.

However, CF causes your sweat to become very salty. As a result, your body
loses large amounts of salt when you sweat. Thus, your doctor may recommend a high-
salt diet or salt supplements to maintain the balance of minerals in your blood.

If you exercise regularly, you may be able to cut back on your CPT. However,
you should check with your doctor first.

Medicines

If you have CF, your doctor may prescribe antibiotics, anti-inflammatory

medicines, bronchodilators, or medicines to help clear the mucus. These medicines
help treat or prevent lung infections, reduce swelling and open up the airways, and thin
mucus. If you have mutations in a gene called G551D, which occurs in about 5 percent
of people who have CF, your doctor may prescribe the oral medicine ivacaftor
(approved for people with CF who are 6 years of age and older).
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 Antibiotics are the main treatment to prevent or treat lung infections. Your
doctor may prescribe oral, inhaled, or intravenous (IV) antibiotics.

Treatments for Advanced Lung Disease

If you have advanced lung disease, you may need oxygen therapy. Oxygen
usually is given through nasal prongs or a mask.

If other treatments haven't worked, a lung transplant may be an option if you

have severe lung disease. A lung transplant is surgery to remove a person's diseased
lung and replace it with a healthy lung from a deceased donor.

Pulmonary Rehabilitation

Your doctor may recommend PR as part of your treatment plan. PR is a broad

program that helps improve the well-being of people who have chronic (ongoing)
breathing problems.

PR doesn't replace medical therapy. Instead, it's used with medical therapy and
may include:

Exercise training
Nutritional counseling
Education on your lung disease or condition and how to manage it
Energy-conserving techniques
Breathing strategies
Psychological counseling and/or group support

PR has many benefits. It can improve your ability to function and your quality of
life. The program also may help relieve your breathing problems. Even if you have
advanced lung disease, you can still benefit from PR.

Treatment for Digestive Problems

CF can cause many digestive problems, such as bulky stools, intestinal gas, a
swollen belly, severe constipation, and pain or discomfort. Digestive problems also can
lead to poor growth and development in children.

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Treatments for Cystic Fibrosis Complications

A common complication of CF is diabetes. The type of diabetes associated with

CF often requires different treatment than other types of diabetes.

Another common CF complication is the bone-thinning disorder osteoporosis.

Your doctor may prescribe medicines that prevent your bones from losing their density.

Living With Cystic Fibrosis

If you or your child has cystic fibrosis (CF), you should learn as much as you
can about the disease. Work closely with your doctors to learn how to manage CF.

Lifestyle Changes

In between medical checkups, you can practice good self-care and follow a
healthy lifestyle.

For example, follow a healthy diet. A healthy diet includes a variety of fruits,
vegetables, and whole grains. Talk with your doctor about what types and amounts of
foods you should include in your diet.

Other lifestyle changes include:

Not smoking and avoiding tobacco smoke

Washing your hands often to lower your risk of infection
Exercising regularly and drinking lots of fluids
Doing chest physical therapy (as your doctor recommends)

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THALASSEMIA

What Are Thalassemias?

Thalassemias are inherited blood disorders. "Inherited" means that the disorder
is passed from parents to children through genes.

Thalassemias cause the body to make fewer healthy red blood cells and less
hemoglobin than normal. Hemoglobin is an iron-rich protein in red blood cells. It
carries oxygen to all parts of the body. Hemoglobin also carries carbon dioxide (a
waste gas) from the body to the lungs, where it's exhaled. People who have
thalassemias can have mild or severe anemia. Anemia is caused by a lower than normal
number of red blood cells or not enough hemoglobin in the red blood cells.

Overview
Normal hemoglobin, also called hemoglobin A, has four protein chainstwo
alpha globin and two beta globin. The two major types of thalassemia, alpha and beta,
are named after defects in these protein chains.

Four genes (two from each parent) are needed to make enough alpha globin
protein chains. Alpha thalassemia trait occurs if one or two of the four genes are
missing. If more than two genes are missing, moderate to severe anemia occurs.

The most severe form of alpha thalassemia is called alpha thalassemia major or
hydrops fetalis. Babies who have this disorder usually die before or shortly after birth.
Two genes (one from each parent) are needed to make enough beta globin protein
chains. Beta thalassemia occurs if one or both genes are altered.

The severity of beta thalassemia depends on how much one or both genes are
affected. If both genes are affected, the result is moderate to severe anemia. The severe
form of beta thalassemia is known as thalassemia major or Cooley's anemia.
Thalassemias affect males and females. The disorders occur most often among people
of Italian, Greek, Middle Eastern, Southern Asian, and African descent. Severe forms
usually are diagnosed in early childhood and are lifelong conditions.

Doctors diagnose thalassemias using blood tests. The disorders are treated
withblood transfusions, medicines, and other procedures.

Outlook

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 Treatments for thalassemias have improved over the years. People who have
moderate or severe thalassemias are now living longer and have better quality of life.

However, complications from thalassemias and their treatments are frequent.

People who have moderate or severe thalassemias must closely follow their treatment
plans. They need to take care of themselves to remain as healthy as possible.

What Causes Thalassemias?

Your body makes three types of blood cells: red blood cells, white blood cells,
and platelets. Red blood cells contain hemoglobin, an iron-rich protein that carries
oxygen from your lungs to all parts of your body. Hemoglobin also carries carbon
dioxide (a waste gas) from your body to your lungs, where it's exhaled.

Hemoglobin has two kinds of protein chains: alpha globin and beta globin. If
your body doesn't make enough of these protein chains or they're abnormal, red blood
cells won't form correctly or carry enough oxygen. Your body won't work well if your
red blood cells don't make enough healthy hemoglobin. Genes control how the body
makes hemoglobin protein chains. When these genes are missing or altered,
thalassemias occur.

Thalassemias are inherited disordersthat is, they're passed from parents to

children through genes. People who inherit faulty hemoglobin genes from one parent
but normal genes from the other are called carriers. Carriers often have no signs of
illness other than mild anemia. However, they can pass the faulty genes on to their
children.People who have moderate to severe forms of thalassemia have inherited
faulty genes from both parents.

Alpha Thalassemias

You need four genes (two from each parent) to make enough alpha globin
protein chains. If one or more of the genes is missing, you'll have alpha thalassemia
trait or disease. This means that your body doesn't make enough alpha globin protein.

If you're only missing one gene, you're a "silent" carrier. This means you won't
have any signs of illness.
If you're missing two genes, you have alpha thalassemia trait (also called alpha
thalassemia minor). You may have mild anemia.

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 If you're missing three genes, you likely have hemoglobin H disease (which
a blood test can detect). This form of thalassemia causes moderate to severe
anemia.

Very rarely, a baby is missing all four genes. This condition is called alpha
thalassemia major or hydrops fetalis. Babies who have hydrops fetalis usually die
before or shortly after birth.

Example of an Inheritance Pattern for Alpha Thalassemia

The picture shows one example of how alpha thalassemia is inherited. The
alpha globin genes are located on chromosome 16. A child inherits four alpha globin
genes (two from each parent). In this example, the father is missing two alpha globin
genes and the mother is missing one alpha globin gene.

Each child has a 25 percent chance of inheriting two missing genes and two
normal genes (thalassemia trait), three missing genes and one normal gene
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(hemoglobin H disease), four normal genes (no anemia), or one missing gene and
three normal genes (silent carrier).

Beta Thalassemias

You need two genes (one from each parent) to make enough beta globin protein
chains. If one or both of these genes are altered, you'll have beta thalassemia. This
means that your body wont make enough beta globin protein.

If you have one altered gene, you're a carrier. This condition is called beta
thalassemia trait or beta thalassemia minor. It causes mild anemia.
If both genes are altered, you'll have beta thalassemia intermedia or beta
thalassemia major (also called Cooley's anemia). The intermedia form of the
disorder causes moderate anemia. The major form causes severe anemia.
Example of an Inheritance Pattern for Beta Thalassemia

The picture shows one example of how beta thalassemia is inherited. The beta
globin gene is located on chromosome 11. A child inherits two beta globin genes (one
from each parent). In this example, each parent has one altered beta globin gene.
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 Each child has a 25 percent chance of inheriting two normal genes (no
anemia), a 50 percent chance of inheriting one altered gene and one normal gene
(beta thalassemia trait), or a 25 percent chance of inheriting two altered genes (beta
thalassemia major).

Who Is at Risk for Thalassemias?

Family history and ancestry are the two risk factors for thalassemias.

Family History

Thalassemias are inheritedthat is, the genes for the disorders are passed from
parents to their children. If your parents have missing or altered hemoglobin-making
genes, you may have thalassemia.

Ancestry

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 Thalassemias occur most often among people of Italian, Greek, Middle Eastern,
Southern Asian, and African descent.

What Are the Signs and Symptoms of Thalassemias?

A lack of oxygen in the bloodstream causes the signs and symptoms of
thalassemias. The lack of oxygen occurs because the body doesn't make enough
healthy red blood cells and hemoglobin. The severity of symptoms depends on the
severity of the disorder.

No Symptoms

Alpha thalassemia silent carriers generally have no signs or symptoms of the

disorder. The lack of alpha globin protein is so minor that the body's hemoglobin works
normally.

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Mild Anemia

People who have alpha or beta thalassemia trait can have mild anemia. However,
many people who have these types of thalassemia have no signs or symptoms.

Mild anemia can make you feel tired.Mild anemia caused by alpha thalassemia
trait might be mistaken for iron-deficiency anemia.

Mild to Moderate Anemia and Other Signs and Symptoms

People who have beta thalassemia intermedia have mild to moderate anemia.
They also may have other health problems, such as:

Slowed growth and delayed puberty. Anemia can slow down a child's growth
and development.
Bone problems. Thalassemia may cause bone marrow to expand. Bone marrow
is the spongy substance inside bones that makes blood cells. When bone marrow
expands, the bones become wider than normal. They may become brittle and
break easily.
An enlarged spleen. The spleen is an organ that helps your body fight infection
and remove unwanted material. When a person has thalassemia, the spleen has
to work very hard. As a result, the spleen becomes larger than normal. This
makes anemia worse. If the spleen becomes too large, it must be removed.

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Severe Anemia and Other Signs and Symptoms

People who have hemoglobin H disease or beta thalassemia major (also called
Cooley's anemia) have severe thalassemia. Signs and symptoms usually occur within
the first 2 years of life. They may include severe anemia and other health problems,
such as:

A pale and listless appearance

Poor appetite
Dark urine (a sign that red blood cells are breaking down)
Slowed growth and delayed puberty
Jaundice (a yellowish color of the skin or whites of the eyes)
An enlarged spleen, liver, or heart
Bone problems (especially with bones in the face)

Complications of Thalassemias

Better treatments now allow people who have moderate and severe thalassemias
to live much longer. As a result, these people must cope with complications of these
disorders that occur over time.

Heart and Liver Diseases

Regular blood transfusions are a standard treatment for thalassemias.

Transfusions can cause iron to build up in the blood (iron overload). This can damage
organs and tissues, especially the heart and liver.

Heart disease caused by iron overload is the main cause of death in people who
have thalassemias. Heart disease includes heart failure, arrhythmias (irregular
heartbeats), and heart attack.

Infection

Among people who have thalassemias, infections are a key cause of illness and
the second most common cause of death. People who have had their spleens removed
are at even higher risk because they no longer have this infection-fighting organ.

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Osteoporosis

Many people who have thalassemias have bone problems, including

osteoporosis. This is a condition in which bones are weak and brittle and break easily.

How Are Thalassemias Diagnosed?

Doctors diagnose thalassemias using blood tests, including a complete blood
count (CBC) and special hemoglobin tests.

A CBC measures the amount of hemoglobin and the different kinds of blood
cells, such as red blood cells, in a sample of blood. People who have
thalassemias have fewer healthy red blood cells and less hemoglobin than
normal in their blood. People who have alpha or beta thalassemia trait may have
red blood cells that are smaller than normal.
Hemoglobin tests measure the types of hemoglobin in a blood sample. People
who have thalassemias have problems with the alpha or beta globin protein
chains of hemoglobin.

How Are Thalassemias Treated?

Treatments for thalassemias depend on the type and severity of the disorder.
People who are carriers or who have alpha or beta thalassemia trait have mild or no
symptoms. Theyll likely need little or no treatment.

Doctors use three standard treatments for moderate and severe forms of
thalassemia. These treatments include blood transfusions, iron chelation therapy, and
folic acid supplements. Other treatments have been developed or are being tested, but
they're used much less often.

Standard Treatments
Blood Transfusions

Transfusions of red blood cells are the main treatment for people who have
moderate or severe thalassemias. This treatment gives you healthy red blood cells with
normal hemoglobin.

Blood transfusions allow you to feel better, enjoy normal activities, and live into
adulthood. This treatment is lifesaving, but it's expensive and carries a risk of

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transmitting infections and viruses (for example, hepatitis). However, the risk is very
low in the United States because of careful blood screening.

Iron Chelation Therapy

The hemoglobin in red blood cells is an iron-rich protein. Thus, regular blood
transfusions can lead to a buildup of iron in the blood. This condition is called iron
overload. It damages the liver, heart, and other parts of the body.

To prevent this damage, doctors use iron chelation therapy to remove excess iron
from the body. Two medicines are used for iron chelation therapy.

Deferoxamine is a liquid medicine that's given slowly under the skin, usually
with a small portable pump used overnight. This therapy takes time and can be
mildly painful. Side effects include problems with vision and hearing.
Deferasirox is a pill taken once daily. Side effects include headache, nausea
(feeling sick to the stomach), vomiting, diarrhea, joint pain, and tiredness.
Folic Acid Supplements

Folic acid is a B vitamin that helps build healthy red blood cells. Your doctor
may recommend folic acid supplements in addition to treatment with blood
transfusions and/or iron chelation therapy.

Other Treatments

Other treatments for thalassemias have been developed or are being tested, but
they're used much less often.

Blood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant replaces faulty stem cells with healthy
ones from another person (a donor). Stem cells are the cells inside bone marrow that
make red blood cells and other types of blood cells.

A stem cell transplant is the only treatment that can cure thalassemia. But only a
small number of people who have severe thalassemias are able to find a good donor
match and have the risky procedure.

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Possible Future Treatments

Researchers are working to find new treatments for thalassemias. For example, it
might be possible someday to insert a normal hemoglobin gene into stem cells in bone
marrow. This will allow people who have thalassemias to make their own healthy red
blood cells and hemoglobin.

Researchers also are studying ways to trigger a person's ability to make fetal
hemoglobin after birth. This type of hemoglobin is found in fetuses and newborns.
After birth, the body switches to making adult hemoglobin. Making more fetal
hemoglobin might make up for the lack of healthy adult hemoglobin.

How Can Thalassemias Be Prevented?

You cant prevent thalassemias because theyre inherited (passed from parents to
children through genes). However, prenatal tests can detect these blood disorders
before birth.

Living With Thalassemias

Survival and quality of life have improved for people who have moderate or
severe thalassemias. This is because:

More people are able to get blood transfusions now.

Blood screening has reduced the number of infections from blood transfusions.
Also, treatments for other kinds of infections have improved.
Iron chelation treatments are available that are easier for some people to take.
Some people have been cured through blood and marrow stem cell transplants.

Living with thalassemia can be challenging, but several approaches can help you cope.

Follow Your Treatment Plan

Following the treatment plan your doctor gives you is important. For example,
get blood transfusions as your doctor recommends, and take your iron chelation
medicine as prescribed.

Iron chelation treatment can take time and be mildly painful. However, don't
stop taking your medicine. The leading cause of death among people who have

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thalassemias is heart disease caused by iron overload. Iron buildup can damage your
heart, liver, and other organs.

Take folic acid supplements if your doctor prescribes them. Folic acid is a B
vitamin that helps build healthy red blood cells. Also, talk with your doctor about
whether you need other vitamin or mineral supplements, such as vitamins A, C, or D or
selenium.

Get Ongoing Medical Care

Keep your scheduled medical appointments, and get any tests that your doctor
recommends.

These tests may include:

Monthly complete blood counts and tests for blood iron levels every 3 months
Yearly tests for heart function, liver function, and viral infections (for example,
hepatitis B and C and HIV)
Yearly tests to check for iron buildup in your liver
Yearly vision and hearing tests
Regular checkups to make sure blood transfusions are working
Other tests as needed (such as lung function tests, genetic tests, and tests to
match your tissues with a possible donor if a stem cell transplant is being
considered)

Children who have thalassemias should receive yearly checkups to monitor their
growth and development. The checkups include a physical exam, including a height
and weight check, and any necessary tests.

Take Steps To Stay Healthy

Take steps to stay as healthy as possible. Follow a healthy eating plan and your
doctor's instructions for taking iron supplements.

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 Get vaccinations as needed, especially if you've had your spleen removed. You
may need vaccines for the flu, pneumonia, hepatitis B, and meningitis. Your doctor will
advise you about which vaccines you need.

Watch for signs of infection (such as a fever) and take steps to lower your risk
for infection (especially if you've had your spleen removed). For example:

Wash your hands often.

Avoid crowds during cold and flu season.
Keep the skin around the site where you get blood transfusions as clean as
possible.
Call your doctor if a fever develops.

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