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CONTENTS

1. Introduction and formation of DNA


2. Discovery of DNA
3. Structure of DNA
4. Genetic disorders
5. Color blindness
6. Down syndrome
7. Cystic fibrosis
8. Haemophilia
9. Hemocromatosis

Introduction and formation of DNA


Deoxyribonucleic acid (DNA) is a nucleic acid that contains
the genetic instructions used in the development and functioning of all
known living organisms and some viruses. The main role of
DNA molecules is the long-term storage of information. DNA is often
compared to a set of blueprints, since it contains the instructions
needed to construct other components of cells, such
as proteins and RNA molecules. The DNA segments that carry this
genetic information are called genes. DNA is organized into long
structures called chromosomes. An important property of DNA is that
it can replicate, or make copies of itself. Each strand of DNA in the
double helix can serve as a pattern for duplicating the sequence of
bases. This is critical when cells divide because each new cell needs to
have an exact copy of the DNA present in the old cell. That is why
chromosomes are duplicated before cells divide, in a process called DNA
replication. Eukaryotic organisms store most of their DNA inside
the cell nucleus and some of their DNA in organelles, such
as mitochondria or chloroplasts. In contrast, prokaryotes store their
DNA only in the cytoplasm. Within the
chromosomes, chromatin proteins such as histones compact and organize
DNA. These compact structures guide the interactions between DNA
and other proteins, helping control which parts of the DNA are
transcribed. Chemically, DNA consists of two long polymers of simple
units called nucleotides, with backbones made
of sugars and phosphate groups joined by ester bonds. These two
strands run in opposite directions to each other and are therefore anti-
parallel. Attached to each sugar is one of four types of molecules
called bases. Together, a base, sugar, and phosphate are called a
nucleotide. Nucleotides are arranged in two long strands that form a
spiral called a double helix. The structure of the double helix is
somewhat like a ladder, with the base pairs forming the ladder’s rungs
and the sugar and phosphate molecules forming the vertical sidepieces
of the ladder. The four types of nitrogen bases found in nucleotides
are: adenine (A), thymine (T), guanine (G) and cytosine (C). The order, or
sequence, of these bases determines what biological instructions are
contained in a strand of DNA. For example, the sequence ATCGTT
might instruct for blue eyes, while ATCGCT might instruct for brown.
This information is read using the genetic code, which specifies the
sequence of the amino acids within proteins. The code is read by copying
stretches of DNA into the related nucleic acid RNA, in a process
called transcription. Human DNA consists of about 3 billion bases, and
more than 99 percent of those bases are the same in all people. Human
DNA consists of about 3 billion bases, and more than 99 percent of
those bases are the same in all people. In sexual reproduction,
organisms inherit half of their nuclear DNA from the male parent and
half from the female parent. However, organisms inherit their entire
mitochondrial DNA from the female parent. This occurs because only
egg cells, and not sperm cells, keep their mitochondria during
fertilization. When DNA becomes altered by a substance known as
a mutagen, it can cause health problems. Some mutagens have an impact
on DNA in the eggs and sperm, or on developing organisms, causing them
to develop birth defects. Others can change living organisms,
contributing to the development of a variety of health problems.
Mutagens often introduce errors at the copying stage, which means
that these errors will be replicated numerous times as the damaged
DNA perpetuates itself.

Discovery of DNA
The identification of DNA and its structure is one of the most
important discoveries of the twentieth century. DNA was first isolated,
analyzed and recognized as a unique macromolecule by Friedrich
Miescher in 1869. Friedrich Miescher, who was an eminent physiological
chemist from Switzerland, isolated this substance from the pus of
discarded surgical bandages. Friedrich called it nuclein, since it was
located in the nucleus of the cells. Using arduous and complicated
procedures, Miescher proved that the new substance did indeed come
from cell nuclei, and that is was a fundamentally new type of organic
molecule unlike anything known at the time. Although Miescher did
develop some hypotheses about how "nuclein" might be involved in
heredity, he ascribed to the view at the time that any one type of
molecule would be too simple to account for all the variation seen within
species. In 1919, Phoebus Levene identified the base, sugar and
phosphate nucleotide unit in the structure. Further, in 1937, William
Astbury produced the first X-ray diffraction patterns that proved that
DNA had a regular structure. In 1928, Frederick Griffith performed
experiments to prove that DNA carried genetic information.
Thereafter, Oswald Avery along with his co-workers identified DNA as
the transforming principle in the year 1943. The role of DNA in
heredity was confirmed in 1952, when Alfred Hershey and Martha
Chase showed that DNA is the genetic material of the T2 phage. Finally
in 1953, James D. Watson and Francis Crick suggested the first
accurate model of DNA structure. Watson, a biologist, and Crick, a
physicist, were working together in a laboratory in Cambridge, England.
Their work focused on the structure of DNA. Pauling, a chemist, had
discovered an important structure of protein in 1951 and Franklin was a
chemist working busily in a laboratory in France at the time. Wilkins, a
physicist from New Zealand, was a director for a biophysics laboratory
at King's College. In 1951, he took the first x-ray pictures of DNA,
which later resulted in his idea that DNA structure could be helical,
similar to the protein structure shown by Pauling but instead it was
incorrect. The mistake was actually based on a falsely recollected
conversation that Watson had with Franklin, when Franklin had said that
she used x-ray crystallography to establish the water content of DNA.
Watson ended up incorrectly recalling the numbers. Finally, Watson and
Crick received Franklin’s photo-51. Shortly thereafter, the model of
DNA was published. It was Meselson-Stahl experiment in 1958, which
led to the final confirmation of the replication mechanism that was
implied by the double-helical structure. The Meselson–Stahl
experiment was an experiment by Matthew Meselson and Franklin
Stahl in 1958 which supported the hypothesis that DNA
replication was semi conservative. Semi conservative replication means
that when the double stranded DNA helix was replicated, each of the
two double stranded DNA helices consisted of one strand coming from
the original helix and one newly synthesized. It has been called "the
most beautiful experiment in biology. Therefore a great discovery of
DNA has come to end.

Structure of DNA
In 1951, 23-year old biologist James Watson traveled from the United
States to work with Francis Crick, an English physicist at the University
of Cambridge. Crick was already using the process of X-ray
crystallography to study the structure of protein molecules. Together,
Watson and Crick used X-ray crystallography data, produced by
Rosalind Franklin and Maurice Wilkins at King's College in London, to
decipher DNA's structure. This is what they already knew from the
work of many scientists, about the DNA molecule:

1. DNA is made up of subunits which scientists called nucleotides.


2. Each nucleotide is made up of a sugar, a phosphate and a base.
3. There are 4 different bases in a DNA molecule: adenine (a
purine), cytosine (a pyrimidine), guanine (a purine) and thymine (a
pyrimidine).
4. The number of purine bases equals the number of pyrimidine
bases
5. The number of adenine bases equals the number of thymine bases
6. The number of guanine bases equals the number of cytosine bases
7. The basic structure of the DNA molecule is helical, with the
bases being stacked on top of each other

Working with nucleotide models made of wire, Watson and Crick


attempted to put together the puzzle of DNA structure in such a way
that their model would account for the variety of facts that they knew
described the molecule. Once satisfied with their model, they published
their hypothesis, entitled "Molecular Structure of Nucleic Acids: A
Structure for Deoxyribose Nucleic Acid" in the British journal Nature
(April 25, 1953. volume 171:737-738.) It is interesting to note that this
paper has been cited over 800 times since its first appearance!

Here are their words:

"...This (DNA) structure has two helical chains each coiled round the
same axis...Both chains follow right handed helices...the two chains run
in opposite directions. ..The bases are on the inside of the helix and the
phosphates on the outside..."

"The novel feature of the structure is the manner in which the two
chains are held together by the purine and pyrimidine bases... The
(bases) are joined together in pairs, a single base from one chain being
hydrogen-bonded to a single base from the other chain, so that the two
lie side by side...One of the pair must be a purine and the other a
pyrimidine for bonding to occur. ...Only specific pairs of bases can bond
together. These pairs are: adenine (purine) with thymine (pyrimidine),
and guanine (purine) with cytosine (pyrimidine)."

"...in other words, if an adenine forms one member of a pair, on either


chain, then on these assumptions the other member must be thymine;
similarly for guanine and cytosine. The sequence of bases on a single
chain does not appear to be restricted in any way. However, if only
specific pairs of bases can be formed, it follows that if the sequence of
bases on one chain is given, then the sequence on the other chain is
automatically determined."
"...It has not escaped our notice that the specific pairing we have
postulated immediately suggests a possible copying mechanism for the
genetic material."

And with these words, the way was made clear for tremendous strides
in our understanding of the structure of DNA and, as a result our
ability to work with and manipulate the information-rich DNA molecule.

Genetic disorders
A genetic disorder is a medical condition that is caused by mutations in
a single gene or within an entire set of genes. These mutations can
happen at any point in life, from mutations within the gamete up until
the biological function of an organism ceases. The body is able to repair
some mutations, and they do not result in disorders. According to the
Genetic Science and Learning Center (GLSC), “our cells have mechanisms
for repairing DNA if mistakes are made in the sequence or if the DNA
is damaged.” Also, some mutations do not exist on both sets of
chromosomes—as in cases where a mutation is only inherited from one
parent—and one normal gene is enough to ensure proper function of the
DNA.
There are four categories of genetic disorders. The first are
chromosomal abnormalities, where a large segment or the entire
chromosome in the DNA is missing, duplicated or otherwise altered, as
is the case with Dawn syndrome and CES. There are also single-gene
disorders, resulting from a mutation that causes the protein product of
a solitary gene to become altered or missing, which is the cause of
sickle cell anemia. Further, there are multifactorial disorders that
occur when mutations affect multiple genes and are often coupled with
environmental causes—this is the case in diseases like diabetes and
cancer. Finally, there are mitochondrial disorders, which are very rare.
These disorders happen when mutations are present in the non-
chromosomal DNA located within the mitochondria.

I. Color blindness
Color blindness or color vision deficiency is the inability to perceive
differences between some of the colors that others can distinguish. It
is most often of genetic nature, but may also occur because
of eye, nerve, or brain damage, or exposure to certain chemicals. The
English chemist John Dalton published the first scientific paper on the
subject in 1798, "Extraordinary facts relating to the vision of
colours", after the realization of his own color blindness. Because of
Dalton's work, the condition was often called daltonism, although this
term is now used for a type of color blindness called deuteranopia.
There are some studies which conclude that color blind individuals are
better at penetrating certain color camouflages and it has been
suggested that this may be the evolutionary explanation for the
surprisingly high frequency of congenital red-green color blindness.
Color vision deficiencies can be classified as acquired or inherited.

• Acquired
• Inherited: There are three types of inherited or congenital color
vision deficiencies: monochromacy, dichromacy, and anomalous
trichromacy.
 Monochromacy, also known as "total color blindness," is the lack
of ability to distinguish colors; caused by cone defect or
absence. Monochromacy occurs when two or all three of the cone
pigments are missing and color and lightness vision is reduced to
one dimension.

 Rod monochromacy (achromatopsia) is an exceedingly rare,


nonprogressive inability to distinguish any colors as a result of
absent or nonfunctioning retinal cones. It is associated with
light sensitivity (photophobia), involuntary eye oscillations
(nystagmus), and poor vision.
 Cone monochromacy is a rare total color blindness that is
accompanied by relatively normal vision, electoretinogram, and
electrooculogram.

 Dichromacy is a moderately severe color vision defect in which


one of the three basic color mechanisms is absent or not
functioning. It is hereditary and, in the case of Protanopia or
Deuteranopia, sex-linked, affecting predominantly
males. Dichromacy occurs when one of the cone pigments is
missing and color is reduced to two dimensions.

 Protanopia is a severe type of color vision deficiency caused by


the complete absence of red retinal photoreceptors. It is a
form of dichromatism in which red appears dark. It is
hereditary, sex-linked, and present in 1% of males.
 Deuteranopia is a color vision deficiency in which the green
retinal photoreceptors are absent, moderately affecting red-
green hue discrimination. It is a form of dichromatism in which
there are only two cone pigments present. It is likewise
hereditary and sex-linked.
 Tritanopia is a very rare color vision disturbance in which
there are only two cone pigments present and a total absence
of blue retinal receptors.

 Anomalous trichromacy is a common type of inherited color vision


deficiency, occurring when one of the three cone pigments is
altered in its spectral sensitivity. This results in an impairment,
rather than loss, of trichromacy (normal three-dimensional color
vision).

 Protanomaly is a mild color vision defect in which an altered


spectral sensitivity of red retinal receptors (closer to green
receptor response) results in poor red-green hue
discrimination. It is hereditary, sex-linked, and present in 1%
of males.
 Deuteranomaly, caused by a similar shift in the green retinal
receptors, is by far the most common type of color vision
deficiency, mildly affecting red-green hue discrimination in 5%
of males. It is hereditary and sex-linked.
 Tritanomaly is a rare, hereditary color vision deficiency
affecting blue-yellow hue discrimination. Unlike most other
forms, it is not sex-linked.
II. Down syndrome

Down syndrome is a chromosomal disorder caused by the presence of all


or part of an extra 21st chromosome. It is named after John Langdon
Down, the British physician who described the syndrome in 1866. The
disorder was identified as a chromosome 21 trisomy by Jerome
Lejeune in 1959. Trisomy 21 is caused by a meiotic nondisjunction event.
With nondisjunction, a gamete is produced with an extra copy of
chromosome 21; the gamete thus has 24 chromosomes. When combined
with a normal gamete from the other parent, the embryo now has 47
chromosomes, with three copies of chromosome 21. Trisomy 21 is the
cause of approximately 95% of observed Down syndromes, with 88%
coming from nondisjunction in the maternal gamete and 8% coming from
nondisjunction in the paternal gamete. The condition is characterized by
a combination of major and minor differences in structure. Often Down
syndrome is associated with some impairment of cognitive ability
and physical growth, and a particular set of facial characteristics. Down
syndrome in a fetus can be identified with amniocentesis during
pregnancy or in a baby at birth. Individuals with Down syndrome tend to
have a lower-than-average cognitive ability, often ranging from mild to
moderate disabilities. A small number have severe to profound mental
disability. The average IQ of children with Down syndrome is around 50,
compared to normal children with an IQ of 100. The incidence of Down
syndrome is estimated at 1 per 800 to 1,000 births, although it is
statistically much more common with older mothers. Other factors may
also play a role. Many of the common physical features of Down
syndrome may also appear in people with a standard set of
chromosomes, including microgenia (an abnormally small chin), an
unusually round face, macroglossia (protruding or oversized tongue), an
almond shape to the eyes caused by an epicanthic fold of the eyelid, up
slanting palpebral fissures (the separation between the upper and lower
eyelids), shorter limbs, a single transverse palmar crease (a single
instead of a double crease across one or both palms, also called the
Simian crease), poor muscle tone, and a larger than normal space
between the big and second toes. Health concerns for individuals with
Down syndrome include a higher risk for congenital heart
defects, gastroesophageal reflux disease, recurrent ear
infections, obstructive sleep apnea, and thyroid dysfunctions. Early
childhood intervention, screening for common problems, medical
treatment where indicated, a conducive family environment, and
vocational training can improve the overall development of children with
Down syndrome. Although some of the physical genetic limitations of
Down syndrome cannot be overcome, education and proper care will
improve quality of life. Down syndrome can result from several
different genetic mechanisms. Individuals with Down syndrome may
have some or all of the following physical
characteristics: microgenia, oblique eye fissures with epicanthic skin
folds on the inner corner of the eyes (formerly known as mongoloid
fold), muscle hypotonia (poor muscle tone), etc. Most individuals with
Down syndrome have mental retardation in the mild (IQ 50–70) to
moderate (IQ 35–50) range,[8] with individuals having Mosaic Down
syndrome typically 10–30 points higher. They also may have a broad
head and a very round face. At birth, kids with Down syndrome are
usually of average size, but they tend to grow at a slower rate and
remain smaller than their peers. For infants, hypotonia may contribute
to sucking and feeding problems, as well as constipation and other
digestive issues. Toddlers and older kids may have delays in speech and
self-care skills like feeding, dressing, and toilet teaching. Down
syndrome affects kids' ability to learn in different ways, but most have
mild to moderate intellectual impairment. Kids with Down syndrome can
and do learn, and are capable of developing skills throughout their lives.
They simply reach goals at a different pace — which is why it's
important not to compare a child with Down syndrome against typically
developing siblings or even other children with the condition. Plastic
surgery has sometimes been advocated and performed on children with
Down syndrome, based on the assumption that surgery can reduce the
facial features associated with Down syndrome, therefore decreasing
social stigma, and leading to a better quality of life. Plastic surgery on
children with Down syndrome is uncommon, and continues to be
controversial.

III. Cystic fibrosis

Cystic fibrosis is a common disease which affects the entire body,


causing progressive disability and often early death. The name cystic
fibrosis refers to the characteristic scarring (fibrosis) and cyst
formation within the pancreas, first recognized in the 1930s. Difficulty
breathing is the most serious symptom and results from frequent lung
infections that are treated, though not cured, by antibiotics and other
medications. A multitude of other symptoms, including sinus
infections, poor growth, diarrhoea, and infertility result from the
effects of CF on other parts of the body. CF is caused by a mutation in
the gene for the protein cystic fibrosis transmembrane conductance
regulator (CFTR). This gene is required to regulate the components of
sweat, digestive juices, and mucus. Although most people without CF
have two working copies of the CFTR gene, only one is needed to
prevent cystic fibrosis. CF develops when neither gene works normally.
Therefore, CF is considered an autosomal recessive disease.
Approximately 30,000 Americans have CF, making it one of the most
common life-shortening inherited diseases. Individuals with cystic
fibrosis can be diagnosed before birth by genetic testing in early
childhood. Mucus is a substance made by the lining of some body tissues.
Normally, mucus is a slippery, watery substance. It keeps the linings of
certain organs moist and prevents them from drying out or getting
infected. However, if you have cystic fibrosis, your mucus becomes
thick and sticky. The mucus builds up in your lungs and blocks your
airways—the 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. Ultimately, lung transplantation is often necessary as CF
worsens. The symptoms of cystic fibrosis vary from person to person
and over time. Sometimes you will have few symptoms. Other times,
your symptoms may become more severe. One of the first signs of
cystic fibrosis (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 cystic fibrosis develop later
and may include infections that block the airways that causes frequent
coughing; frequent bouts of sinusitis, bronchitis, and pneumonia;
pneumothorax; diarrhoea; foul-smelling, greasy stools; severe
constipation; pancreatitis; rectal prolapse; liver disease; diabetes;
gallstones; infertility and dehydration. Cystic fibrosis also causes your
sweat to become very salty. As a result, your body loses large amounts
of salt when you sweat. This can upset the balance of minerals in your
blood and cause a number of health problems. Examples
include dehydration (a condition in which your body doesn't have enough
fluids), increased heart rate, tiredness, weakness, decreased blood
pressure, heat stroke, and, rarely, death. The aim of CF treatment is to
keep the lungs clear of mucus and free of infection. It's also important
for someone with CF to eat well. Gene therapy has been explored as a
potential cure for cystic fibrosis. Ideally, gene therapy attempts to
place a normal copy of the CFTR gene into affected cells. Transferring
the normal CFTR gene into the affected epithelium cells would result in
the production of functional CFTR in all target cells, without adverse
reactions or an inflammation response. Studies have shown that to
prevent the lung manifestations of cystic fibrosis, only 5–10% the
normal amount of CFTR gene expression is needed. Multiple approaches
have been tested for gene transfer, such as liposomes and viral vectors
in animal models and clinical trials. However, both methods were found
to be relatively inefficient treatment options. The main reason is that
very few cells take up the vector and express the gene, so the
treatment has little effect. Additionally, problems have been noted in
DNA recombination, such that the gene introduced by the treatment is
rendered unusable.
IV. Hemochromatosis

Hemochromatosis (HHC) is a leading cause of iron overload disease.


People with Hemochromatosis absorb extra amounts of iron from the
daily diet. The human body cannot rid itself of extra iron. Over time,
these excesses build up in major organs such as the heart, liver,
pancreas, joints and pituitary. If the extra iron is not removed,
these organs can become diseased. Untreated hemochromatosis can
be fatal. Iron is an essential nutrient found in many foods. Iron
carries oxygen (in hemoglobin) to all parts of the body. Normally,
humans absorb about 8-10% of the iron in foods that they eat.
People with HHC can absorb four times that amount. Individuals with
hemochromatosis absorb too much iron from the diet. Iron cannot be
excreted therefore the metal can reach toxic levels in tissues of
major organs such as the liver, heart, pituitary, thyroid, pancreas,
and synovium (joints). Therefore, undiagnosed and untreated HHC
increases the risk for diseases and conditions such as diabetes
mellitus, irregular heart beat or heart attack, arthritis
(osteoarthritis, osteoporosis), cirrhosis of the liver or liver cancer,
depression, impotence, infertility, hypothyroidism, hypogonadism, and
some cancers. Chronic fatigue and joint pain are the most common
complaint of people with hemochromatosis. Other common symptoms
include, lack of energy, abdominal pain, loss of sex drive, and heart
flutters or irregular heart beat. Symptoms usually begin in men in
their late 20’s to early 30’s. In women, symptoms usually start about
10-15 years after they stop having a period. If hemochromatosis is
not found early and treated, iron may accumulate in body tissues
causing disease such as:

• arthritis (osteoarthrithis, osteoporosis) knuckles, ankles and hips


• liver disease, including an enlarged liver, cirrhosis, cancer, and
liver failure diabetes
• heart problems ( irregular heart beat, heart attack or heart
failure)
• impotence
• infertility
• loss of period or early menopause
• abnormal skin color, ashen gray-green or reddish-bronze
• hypothyroidism (which can cause depression)

Hemochromatosis can be overlooked by a doctor who is concentrating


on treatment of diseases that are present in the patient. Genetic
tests can confirm a diagnosis and can help identify family members
who are at risk for hemochromatosis. Type I hemochromatosis,
which occurs in adults, is caused by defects in the HFE gene. HFE
has many purposes, but one important role is that it helps to control
the amount of iron that is absorbed from food. There are several
known defects in the HFE gene, but two defects are most often
found in people with hemochromatosis. These two defects are called
C282Y and H63D. Everyone has two copies of HFE, one from Mom
and one from Dad. A person can have two normal copies, one normal
and one changed (mutated or mutation) copy; two copies of the same
mutation; or two different mutated copies. When a person has one
mutated copy, he or she is called a carrier or heterozygote. When a
person has two of the same mutated copies, he or she is called a
homozygote. When a person has two different, but mutated, copies,
he or she is called a compound heterozygote. Several other genes
and proteins that work with HFE have been discovered. These are
called modifiers. Scientists are studying HFE and its modifiers to
learn why some people get sick and others do not. It is very
important to get iron levels down to normal. Therapeutic blood
removal or phlebotomy is used to accomplish this. It is the same as
regular blood donation but TP requires a doctor’s order
(prescription). Regular blood donation can be done every 8 weeks. A
person with severe iron overload may need to give blood as much as 8
times in a single month! The goal is to bring blood ferritin levels to a
normal range of 25 to 75ng/mL. Once iron levels reach normal, a
person can begin maintenance therapy, which involves giving a pint of
blood every 2 to 4 months for life. The TS% and serum ferritin
tests can be done periodically to help determine how often blood
should be removed. When hemochromatosis is diagnosed early and
treated before organs are damaged a person can live a normal life
expectancy. For people who have disease at the time of diagnosis,
life expectancy may be shortened depending upon the disease.

V. Haemophilia

Haemophilia is a group of hereditary genetic disorders that impair the


body's ability to control blood clotting or coagulation, which is used to
stop bleeding when a blood vessel is broken. Haemophilia A is the most
common form of the disorder, occurring at about 1 in 5,000–10,000 male
births. Haemophilia B occurs at about 1 in about 20,000–34,000 male
births. Similarly to most recessive sex-linked, X chromosome disorders,
haemophilia is more likely to occur in males than females. This is
because females have two X chromosomes while males have only one,
lacking a 'back up' copy for the defective gene; meaning, the defective
gene is guaranteed to manifest in any male who carries it. Because
females have two X chromosomes and because haemophilia is rare, the
chance of a female having two defective copies of the gene is very low,
thus females are almost exclusively asymptomatic carriers of the
disorder. Female carriers may inherit the defective gene from their
mother, father, or it may be a new mutation. Only under rare
circumstances do females actually have haemophilia. Haemophilia lowers
blood plasma clotting factor levels of the coagulation factors needed
for a normal clotting process. Thus when a blood vessel is injured, a
temporary scab does form, but the missing coagulation factors
prevent fibrin formation, which is necessary to maintain the blood clot.
Thus a haemophiliac does not bleed more intensely than a normal person,
but can bleed for a much longer amount of time. In severe haemophiliacs
even a minor injury could result in blood loss lasting days, weeks, or not
ever healing completely. In areas such as the brain or inside joints, this
can be fatal or permanently debilitating. The major signs and symptoms
of haemophilia are bleeding and bruising. Internal bleeding is common in
people with severe haemophilia. If not treated promptly, internal
bleeding can lead to damaged joints, muscles, or other parts of the
body.
The extent of bleeding depends on the type and severity of the
condition:
• Children with very mild haemophilia may not have noticeable
symptoms for years. Often, the first sign is heavy bleeding from
a dental procedure, an accident, or surgery.
• Children with mild to moderate haemophilia may not have any
signs or symptoms at birth.
• Males with severe haemophilia may bleed heavily after
circumcision.
In most children, the first signs are:
• Heavy bruising and bleeding from the gums as they cut their baby
teeth
• Bumps and bruises from frequent falls as they learn to walk
• Swelling and bruising from bleeding in the joints, soft tissue, and
muscles
Females who are carriers usually have enough clotting factors from
their one normal gene to prevent serious bleeding problems. Bleeding in
the joints is the most common problem in persons with severe
haemophilia. Bleeding often occurs without an injury. It can go on for
days if not treated. However, people with haemophilia can learn to
recognise early symptoms of bleeding in the joints and get treatment
quickly. Early treatment can help limit damage to the joints.
Although bleeding can occur in any joint, the most common places are
the knees, elbows and ankles. The main treatment for haemophilia is
replacement therapy - giving or replacing the clotting factor that is too
low or missing. The type of treatment you receive depends on several
things, including whether you have mild, moderate, or severe
haemophilia.
• Mild haemophilia. Replacement therapy is usually not needed for
mild haemophilia; however, a medicine called desmopressin
(DDAVP) is sometimes given to raise the body's levels of factor
VIII. Since the effect wears off with chronic use, it is applied
only in certain situations (for example, prior to dental work or
participation in sports) to prevent or reduce bleeding.
Desmopressin does not help in haemophilia B.
• Moderate haemophilia. You may need treatment only when
bleeding occurs. You will need to learn to recognise signs and
symptoms of bleeding so that you can get treatment as quickly as
possible. You may also have treatment to prevent bleeding that
could occur when participating in some activity.
• Severe haemophilia. You usually need long-term or shorter term
preventive therapy to prevent bleeding that could cause
permanent damage to your joints, muscles, or other parts of the
body. Some people with severe haemophilia receive treatment only
when bleeding occurs, however.
When bleeding occurs, it is important to get treatment as soon as
possible. Delayed treatment can lead to complications. Learn to
recognise signs of bleeding, and make sure that it is treated quickly.