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Health and diseases_non-communicable diseases_genetic diseases P.1
Genetic diseases--Inborn ‘Errors’ of Metabolism
A. Defects in genes
1. G6PD- an enzyme deficiency
(G6PD) Glucose-6-Phosphate Dehydrogenase deficiency is the most common human enzyme
deficiency; an estimated 400 million people worldwide are affected. One benefit of having G6PD
deficiency is that it confers a resistance to malaria. G6PD deficiency is also referred to as favism since some
G6PD deficient individuals are also allergic to fava beans. Reduced G6PD activity are potentially
serious (even causing death) if they are not properly treated.
A. GENETICS OF G6PD DEFICIENCY
The gene for the G6PD enzyme is located on the X-chromosome.
Q. What can you infer from this information?
G6PD deficiency is known to have over 400 variant alleles. A mutant G6PD enzyme may be different
from person to person; mutations can be in the form of point mutations or can range from one to several
base pair deletions as well as replacements in the DNA.
Q. What is the meaning of ‘variant alleles’
African Americans and some isolated tribes in Africa and Southeast Asia exhibit the highest frequency
of incidence. The incidence in HK is 4.5 in 100 newborn babies.
B. PHYSIOLOGY OF G6PD
an oxidation/reduction reaction. G6PD enzyme functions in
catalyzing the oxidation of glucose-6-phosphate to 6-phosphogluconate, while
concomitantly reducing nicotinamide adenine dinucleotide phosphate (NADP + to NADPH).
The G6PD enzyme catalyzes
This is the first step in the pentose
phosphate pathway. This pathway produces the 5-carbon sugar,
ribose, which is an essential component of both DNA and RNA. There are other metabolic pathways,
however, that can produce ribose if there is a deficiency in G6PD.
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Health and diseases_non-communicable diseases_genetic diseases P.2
In addition to producing the 5-carbon sugar ribose, G6PD is also responsible for maintaining adequate levels
of NADPH
inside the cell. NADPH is a required cofactor in many biosynthetic reactions. NADPH is also
used to keep glutathione, a tri-peptide, in its reduced form:
Reduced glutathione acts as a scavenger for dangerous oxidative metabolites in the
cell; it converts harmful hydrogen peroxide to water. There are other metabolic pathways that can
generate NADPH in all cells, except in red blood cells where other NADPH-producing enzymes are lacking. This
has a profound effect on the stability of red blood cells since they have
only one NADPH-producing
enzyme to remove these harmful oxidants.
This is why G6PD deficient individuals are not prescribed oxidative drugs, because the red blood cells in
these individuals are not able to handle this stress and consequently haemolysis ensues.
Q. What are the importance of G6PD to body cells?
Q. Why are red blood cells particularly susceptible to damage by oxidative drugs or metabolites?
Q. What are the possible consequences of haemolysis on the body?
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Health and diseases_non-communicable diseases_genetic diseases P.3
C. ASPECTS OF G6PD DEFICIENCY
i)
NEONATAL JAUNDICE
itself immediately after
birth. Neonatal jaundice is a common condition in all newborns, but when it persists, G6PD
deficiency is suspected. Neonatal jaundice is a yellowish discoloration of the whites of the eyes, skin,
One of the problems experienced by G6PD deficient individuals presents
and mucous membranes caused by deposition of bile salts in these tissues. This is a direct result of
insufficient activity of the G6PD enzyme in the liver. In some cases, the neonatal jaundice is
severe enough to cause death or permanent neurologic damage.
ii) HAEMOLYTIC ANAEMIA
An anaemic response can be induced in affected individuals by
certain oxidative drugs including
naphthalene, fava beans, or infections. Death ensues if the haemolytic episode is not properly
prohibited from
taking certain drugs. The common theme shared among all of these drugs is that they are oxidizing
agents. In G6PD deficient individuals, oxidative stress may result in the denaturation, or unfolding, of the
haemoglobin molecule. This results in the loss of biological function with respect to
treated. In order to prevent a severe reaction or even death, G6PD deficient individuals are
haemoglobin and leads to the inability of the red blood cell to effectively transport oxygen throughout the body. A
physician should always be consulted before any medications are taken.
Primaquine, one of the first anti-malarial drugs, was the first drug to be implicated in inducing an anaemic
response. It is interesting to note that a deficiency in G6PD has been shown to sometimes confer a
resistance to the malaria-causing parasite, Plasmodium falciparum. This resistance is due to
the fact that the parasite selectively infects red blood cells. In G6PD deficient red blood cells, an essential
metabolite for the survival of the parasite is present in insufficient quantities. This is due to decreased activity of
G6PD within these cells which ultimately leads to the death of the parasite.
Fava beans were the first, and only food product, to be implicated in inducing an anaemic
response in G6PD deficient individuals. Inhaling the pollen of the fava bean plant can also induce haemolysis
in favic individuals. Since some G6PD deficient individuals are allergic to fava beans, the deficiency is
therefore sometimes referred to as favism.
Outside the areas where favism is prevalent, infection is probably the most common cause of haemolysis in
subjects with G6PD deficiency. Oxidative
metabolites produced by numerous bacterial
and viral have been identified as the cause of the anaemic response. Particularly important infections that can
precipitate a haemolytic episode are viral hepatitis, pneumonia, and typhoid fever.
Q. What are the three major factors that can trigger hemolytic anaemia for G6PD deficient persons?
D. TREATMENT
Treatments for neonatal jaundice and haemolytic anaemia have existed for many years. These treatments
insure that the body tissues will be provided
with enough oxygen by the red blood cells. Infants
with prolonged neonatal jaundice are placed under special lights, called bili-lights, which alleviate the jaundice.
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Health and diseases_non-communicable diseases_genetic diseases P.4
nasal oxygen and are placed on bed
rest, which may afford symptomatic relief. Anaemic individuals sometimes need blood transfusions.
When an anaemic episode occurs, individuals are treated with
Q. Genetic engineering is offering a hope to remove the worry of favism from G6PD, suggest how?


日常生活方面要注意：
o
避免吃蠶豆
o
避免接觸樟腦丸
o
不要使用龍膽紫 (紫藥水)
有病應找醫生診療，不可亂服成藥(包括中藥和西藥)，避免使用很多，主要有：
o
解熱及止痛劑：如 Aspirin 亞氏匹寧, Acetanilide, Acetophenetidin(Phenacetin), Antipyrine, Aminopyrine,
p-Aminosalicylic acid

o
抗生素：磺胺劑 Sulfonamides, choramphenicol, sulphones, Nitrofurantoin, Furazolidone, PAS
o
維他命 C (ascorbic acid), 維他命 K1
o
抗瘧藥物，如 Choroquine, Primaquine, Mepacrine, Pamaquine, Pentaquine, Plasmoquine
o
其他 Quinidine, Dimercaprol, Naphthalene Methylene blue, 龍膽紫, Phenylhydrazine, Probenecid
o
中藥包括川蓮，蠟梅花，牛黃...(可能還些未研究清楚)
細菌或病毒感染亦可引起溶血，尤其是年紀小的。
2. Haemophilia
Haemophilia is a lifelong bleeding disorder that prevents blood from clotting properly. Blood
contains many proteins, called clotting factors, which work to stop bleeding. In people with bleeding
disorders, these clotting factors are missing or do not work as they should. The severity of a person’s
haemophilia depends on the amount of clotting factor that is missing.
A person with haemophilia does not bleed faster than anyone else, but bleeding may
last longer. The main
danger is uncontrolled internal bleeding that starts spontaneously or results from injury. Bleeding
into joints and muscles can cause stiffness, pain, severe joint damage, disability, and sometimes death.
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Health and diseases_non-communicable diseases_genetic diseases P.5
A. THE GENETICS DISORDER PASSING FROM MOTHER TO SON
i) X-linked inheritance
Haemophilia is usually inherited and about one in every 5,000 males is
born with the disorder. Worldwide, an estimated 500,000 people live with some
form of haemophilia.
The haemophilia
gene is carried on the X chromosome. As
women have two X chromosomes (XX), the mutated gene would have to
be present on both chromosomes to cause the disease, and this is exceedingly
rare. Since men have only
one X chromosome (XY), one copy of
the mutated haemophilia gene is enough to cause the disease, so males who
inherit the gene will be affected.
ii) Haemophilia and Families
Haemophilia runs
in families; it is passed on from parents to their
children. Complete the following chart to show a person's chances of developing haemophilia:
Mother
Father
Descendents
Carrier (possesses
Normal clotting factor
Fifty percent chance son will have haemophilia.
haemophilia gene)
genes
Fifty percent chance daughter will be a "carrier."
Normal clotting factor genes Haemophilia
Carrier
Haemophilia
iii) Spontaneous genetic mutation
no family
history can be traced in one third of haemophilia A cases. In these cases, a spontaneous
Although a family history of blood clotting factor difficulties is important, it should also be noted that
genetic mutation is assumed to be the cause.
B. TYPES OF HAEMOPHILIA
Two main varieties of haemophilia exist. Haemophilia A is responsible for 80% of all cases. The genetic
disorders responsible for haemophilia A result in low levels or abnormal production of the clotting protein factor
VIII. Haemophilia B, the second most common form of haemophilia, affects factor IX proteins and
accounts for almost 20% of haemophilia cases.
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Health and diseases_non-communicable diseases_genetic diseases P.6
B. WHAT ARE THE SIGNS OF HAEMOPHILIA?




big bruises;
bleeding into muscles and joints, especially the knees, elbows and ankles;
sudden bleeding inside the body for no clear reason;
prolonged bleeding after a cut, tooth removal, surgery or an accident.
Haemophilia symptoms may be mild, moderate, or severe, depending on the amount of clotting
factors produced.
Levels of
clotting factor
Haemophilia
levels
Symptoms
(% of normal level)
mild,
6-30% percent
a concern only when surgery or dental work is required.
moderate
1-5% percent
easy bruising and bleeding.
severe
less than 1% percent
Spontaneous joint bleeding can cause severe pain and physical
deformity as cartilage and surrounding bones are damaged.
Further, gastrointestinal, urinary tract, or intracranial bleeding
can occur and require immediate medical attention. Even mild
physical trauma to the head may result in intracranial bleeding, a
very serious condition.
D. HOW IS HAEMOPHILIA TREATED?
Replacing Blood Factors
Haemophilia is treated by supplementing low levels of blood factor proteins with healthy
replacement clotting proteins. These proteins are most often administered intravenously so that the
clotting factors enter the bloodstream directly and are spread quickly throughout the body.
The frequency of treatment depends on the severity of the haemophilia symptoms. Mild haemophilia may
only require blood factor replacement before surgery or dental work. Severe haemophilia may
require prophylactic (preventive) treatment: blood factors are replaced several times a week to
prevent bleeding incidents.
Q.
One problem of replacement clotting proteins is that they can be inhibited by the immune system.
possible explanation.
Suggest a
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Health and diseases_non-communicable diseases_genetic diseases P.7
Q.
What can be done to the adverse effect of the inhibitor problem?
Q.
Are there effective treatments for haemophilia?
Is there a cure at the moment?
E. AVOIDING COMPLICATIONS OF HAEMOPHILIA
i)
Helpful advices
Decide whether the following are correct advice for people with haemophilia? Explain
·

Advice
Explanation
Check with a physician before taking any form
of medication.

Avoid medications specifically designed to thin the
blood e.g. some painkiller such as aspirin.

Good dental hygiene

Avoid exercises
ii) Hepatitis C and HIV
During the 1980s, haemophilia was treated by replacing low levels of clotting factors with blood
plasma
pooled from thousands of donors. This strategy, although an effective treatment for haemophilia,
proved to have serious safety issues. Viral agents, especially
hepatitis C and HIV, were passed on
to people with haemophilia through the pooled plasma. By the time the health risk was discovered, almost 70%
percent of people treated with pooled plasma or infected
and almost 100% of people were infected with hepatitis
blood products had contracted HIV
C in the 1980s.
Q. What was introduced later to reduce the incidence of HIV and hepatitis C infections?
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Health and diseases_non-communicable diseases_genetic diseases P.8
F. RESEARCHING NEW TREATMENT METHODS - GENE THERAPY
The future of Haemophilia Treatment may be Gene
Therapy
Haemophilia could be cured if clinical trials discover a way to replace
or "repair" the defective gene.
Haemophilia gene therapy research seeks to replace the
defective gene with a normal, fully functional, gene.
Researchers have been successful in developing healthy replacement
genes for use in haemophilia clinical trials. These genes will be
carried into the body using a vector.
Most vectors are harmless viruses that are able to insert the new
DNA into cells. The virus "infects" cells with the healthy gene,
overriding the mutated haemophilia gene. In clinical trials, gene vectors have been used to cure lab
animals of haemophilia A and B. The body's immune system does not appear to release antibody inhibitors
when gene therapy is used.
Q.
Why is haemophilia a good candidate for gene therapy research?
Q.
What are the problems facing researchers in haemophilia gene therapy research?
Haemophiliacs in vCJD scare
January 30, 2001
LONDON, England (CNN) -- Haemophiliacs in the UK who fear they have been
exposed to plasma derived from a blood donor later found to have the human
form of mad cow disease are being urged to contact their doctors.
The blood plasma is said to have been distributed only in "tiny amounts" only after
the donor was found to have the new variant Creutzfeldt-Jakob disease (vCJD).
No simple test exists for vCJD and it has not been proven that the ailment can be
transmitted through blood or blood products. Health experts do not know how many UK haemophiliacs could be at risk
from the vCJD infected blood, which was used before tighter controls were introduced in 1998.
This has come as a devastating shock to the haemophiliac community who have already been stricken by HIV and Hepatitis
C infection. The best advice from experts is that any link between blood, blood products and the transmission of vCJD is
purely theoretical.
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Health and diseases_non-communicable diseases_genetic diseases P.9
3. Sickle cell anaemia
Sickle cell anaemia is a genetic
disease which, under certain circumstances,
causes the red blood cells of a sufferer to be shaped like sickles, instead of
the normal rounded shape. This causes the cells to become stuck in
capillaries which deprives affected tissues of oxygen.
mutation in the β-globin chains of
haemoglobin, replacing glutamic acid with less polar valine at the sixth amino
acid position.
Sickle cell anaemia is caused by a
The mutant
haemoglobin S polymerises under low oxygen conditions causing
distortion of red blood cells.
painful attacks, eventually leading to damage of some
internal organs, stroke, or anaemia, and usually resulting in decreased lifespan. It is
common in countries with a high incidence of malaria, and especially in West Africa.
The disease usually occurs in periodic
A. GENETICS
The
allele responsible for sickle cell anaemia is
incompletely (autosomal) recessive.
defective gene from both father
and mother develops the disease; a person who receives one
defective and one healthy allele remains healthy, but can
pass on the disease and is known as a carrier.
A person who receives the
If two parents who are carriers have a child, there is a 1-in-4
chance of their child developing the illness and a 1-in-2 chance of
their child just being a carrier.
C. CONSEQUENCES
mutation of a single nucleotide (U to A) of the β-globin gene, which
results in glutamic acid to be substituted for valine at position 6. This is normally a benign mutation, causing no
The gene defect is a known
apparent effects on the secondary, tertiary, or quaternary structure of hemoglobin. What it does allow for, under
conditions of low
oxygen concentration, is the polymerization of the HbS itself.
homozygous
for HbS, the presence of long chain polymers of HbS distort the shape of the red
In people heterozygous for HbS (carriers), the polymerization problems are minor. In people
blood cell. Carriers only have symptoms if they are deprived of oxygen (for example, climbing
a mountain) will they develop symptoms.
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D. THE EVOLUTION OF SICKLE CELL ANAEMIA
usually die young and yet the disease is not eliminated from the gene
pool by natural selection. This is because carriers are relatively resistant to malaria. Carriers of
the allele have an unsymptomatic condition called sickle cell trait. Since the gene is incompletely
The sufferers of the illness
recessive, carriers have a few sickle red blood cells at all times, not enough to cause symptoms, but enough to
higher fitness than either of the
homozyogotes. This is known as heterozygote advantage.
give resistance to malaria. Because of this, heterozygotes have a
Q. What does it mean by an ‘unsymptomatic’ trait? Explain in term of the situation in sickle cell anaemia.
In areas where malaria is a problem, people's chances
of survival actually increase if they
carry sickle cell anaemia. Due to the above phenomenon, the illness is still prevalent, especially among
people with recent ancestry in malaria-striken areas, such as Africa, the Mediterranean, India and the
Middle East. In fact, sickle-cell anaemia is the most common genetic disorder among African Americans;
about 1 in every 12 is a carrier.
Q.
In the USA, where there is no endemic malaria, what would you predict about the incidence of sickle cell
anaemia amongst people of African descent compared to those in West Africa?
E. COMPLICATIONS
Sickle cell anaemia can lead to various
complications
complications, including:
explanations
Stroke
Anemia
gallstones
F. TREATMENT
Painful sickle crises are treated symptomatically with painkillers; in cases of severe hemolysis,
exchange transfusion may be required; this is the removal of the patient's blood and replacing it with
non-sickle donor blood.
One interesting treatment is the use of a drug (hydroxyurea) that reactivating
foetal haemoglobin
production in place of the haemoglobin S that causes sickle cell anaemia. There is some concern that
long-term use may be harmful, but it is likely that the benefits outweigh the risks.
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Health and diseases_non-communicable diseases_genetic diseases P.11
4. Alcohol sensitivity and Isozymes (polymorphism)
Isozymes are different molecular forms of enzyme catalyzing the same reaction, usually
with different activity. The alcohol metabolizing enzymes, alcohol dehydrogenase
(ADH) and aldehyde dehydrogenase (ALDH), exist in a number of isozymes. The racial
differences in their isozyme pattern may account for the racial differences (variants)
concerning alcohol sensitivity.
After drinking, most of the ingested alcohol is
metabolized by liver ADH to form
acetaldehyde which is then oxidized to
acetate by ALDH.
Acetaldehyde is responsible for the unpleasant
symptoms of alcohol sensitivity. Its level
is regulated by the activities of ADH and
ALDH.
Most Caucasians have inactive ADH and
active ALDH; hence after drinking, acetaldehyde
is maintained at a low level. In contrast, while
most Orientals have active ADH, -50% are
deficient in ALDH. For this group, after
drinking, acetaldehyde accumulates and results in unpleasant feelings. Such intolerance acts as a
negative reinforcement for heavy alcohol ingestion and probably explains the low
incidence of alcoholism among Orientals.
Q. Study the diagram on the right, suggest how might
the alcohol sensitizing drug works to bring about
improvement in people with problem of alcoholism?
Q.
Ethylene glycol poisoning: ethylene glycol is a
clear, colorless, odorless liquid with a sweet taste.
Ethylene Glycol poisoning
It is
found most commonly in antifreeze, automotive cooling
CH2OH
ADH
CHO
CO2H
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Health and diseases_non-communicable diseases_genetic diseases P.12
systems, and hydraulic brake fluid and as a solvent.
Many cases of ethylene glycol poisoning are due to the
CH2OH
CH2OH
Ethylene glycol
CO2H
Oxalis acid
accidental ingestion of it by children.
They may take in large amounts since the substance tastes good. Alcoholics may also drink it as a substitute for
alcohol (ethanol). Ethylene glycol is itself relatively nontoxic. Its toxicity is related to its metabolized products
such as oxalis acid (crystals) which can cause kidney damage.
ADH.
The metabolism of Ethylene glycol involves
Suggest how consumption of alcoholic drinks might help to relieve the toxicity of ethylene glycol?
Suggest Another treatment for acute Ethylene glycol poisoning.
B. Defects in chromosome – e.g. Down syndrome
It was 1866 that Dr John Langdon Down first remarked on the
facial similarities of a group of his mentally retarded patients.
Unfortunately, he used racial descriptors such as "mongol" to
describe their appearance. With the identification of the
chromosomal basis of Down syndrome in 1959, trisomy
21 was gradually being accepted as a variation of normal.
Down syndrome is the commonest identifiable cause of
intellectual disability, accounting for almost 1/3 of cases.
It occurs equally in all races with an overall incidence of approximately 1
Q.
Q.
in 800 births.
This is much lower than the actual conception rate of Down syndrome individuals. Why?
There is an increase in incidence with advancing maternal age but most children with Down
syndrome are born to mothers who are less than 30. Why ?
A. CAUSES OF DOWN SYNDROME
Down syndrome is usually caused by an error in cell division called non-disjunction. However, two other
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Health and diseases_non-communicable diseases_genetic diseases P.13
types of chromosomal abnormalities, mosaicism and translocation, are also implicated in Down
syndrome - although to a much lesser extent. Regardless of the type of Down syndrome which a person may
have, all people with Down syndrome have an extra, critical portion of the number 21
chromosome present in all, or some, of their cells. This additional genetic material alters the course
of development and causes the characteristics associated with the syndrome.
a.
Nondisjunction
Nondisjunction is a faulty cell division which results in an
embryo with three number 21 chromosomes instead of two. Prior
to, or at, conception, a
pair of number 21
chromosomes, in either the sperm or the egg, fail to
separate. As the embryo develops, the extra chromosome is
replicated in every
cell of the body. This faulty cell division is
responsible for 95 percent of all cases of Down syndrome.
Why nondisjunction occurs is currently unknown, although it does
seem to be related to advancing maternal age. Although
nondisjunction can be of paternal origin, this occurs less frequently.
Q.
Define non-disjunction.
b.
Mosaicism
What are the consequences of non-disjunction?
Mosaicism occurs when nondisjunction of the 21st chromosome takes place in one of the initial cell divisions
after fertilization. When this occurs, there is a mixture of two types of cells, some
containing 46 chromosomes and some containing 47. Those cells with 47 chromosomes contain
an extra 21st chromosome. Because of the "mosaic" pattern of the cells, the term mosaicism is used.
Mosaicism is rare, being responsible for only one to two percent of all cases of Down syndrome.
c.
Translocation
Translocation is a different type of chromosomal problem and occurs in only three to four percent of people with
part of the number 21 chromosome breaks off during cell
division and attaches to another chromosome. While the total number of chromosomes in the
Down syndrome. Translocation occurs when
cells remains 46, the presence of an extra part of the number 21 chromosome causes the features of Down
syndrome. As with nondisjunction trisomy 21, translocation occurs either prior to or at conception.
Unlike nondisjunction, maternal age is not linked to the risk of translocation. Most cases are
sporadic,
chance events. However, in about one-third of cases, one parent is a carrier of a translocated chromosome.
For this reason, the risk of recurrence for translocation is higher than that of nondisjunction. Genetic
counseling can be sought to determine the origin of the translocation.
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Health and diseases_non-communicable diseases_genetic diseases P.14
95% of cases of Down syndrome are caused by trisomy 21, with unbalanced translocations of
chromosome 21 and mosaicism accounting for the remainder. The extra chromosome is maternal in origin in at
least 90% of cases.
B. PRENATAL SCREENING:
a.
Amniocentesis:
Amniocentesis of "high-risk" pregnancies at 16 weeks remains the commonest method of detecting those which
greater than
35 years or a previously affected pregnancy. The procedures include an accidental miscarriage rate
are affected by trisomy 21. Such pregnancies are selected on the basis of maternal age being
of 0.5 - 1%.
Despite being extremely sensitive this test will still miss the majority of trisomy 21 pregnancies due
to the restriction of its use to the older age group, whereas most babies with Down syndrome are born to mothers
less than 30 years old. The use of mass
maternal serum screening (ideally measuring
alphafetoprotein, hCG and oestriol) at 16 weeks gestation is now routine in some states and allows the detection
of 60% of trisomy 21 affected pregnancies with a false positive rate of 5%. Women who are detected in
this way (1-2% of the tested population) are then offered amniocentesis.
Q.
Despite being extremely sensitive, the use of Amniocentesis is restricted to the older age group mother and
only to those screened positive in maternal serum screening.
Why?
Q.
Suggest one disadvantage of Amniocentesis in relation to its late administration at 16 week of gestation.
b.
Chorionic Villus Sampling
This procedure involves the transvaginal biopsy of the developing
placenta at 10 to 12 weeks gestation. It
has the advantage of earlier detection of chromosomal abnormalities than is possible with amniocentesis
but it is associated with a higher rate of post-procedure miscarriage (2-5% depending on the operator).
c.
Ultrasound
Multiple foetal characteristics have been studied as possible indicators of trisomy 21. Although this technology
offers promise for the future, it is not reliable enough for use as a screening test at present. The same can
be said of detecting and karyotyping fetal cells in maternal circulation, although this technology is imminent.
Q.
What do you think are the criteria for a good prenatal diagnostic test for congenital disorder?
d. How is Down syndrome diagnosed in a newborn?
There are many physical characteristics which form the basis for suspecting an infant has Down
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Health and diseases_non-communicable diseases_genetic diseases P.15
syndrome. Many of these characteristics are found, to some extent, in the general population of individuals who
do not have Down syndrome. Hence, if Down syndrome is suspected, a
karyotype will be performed to
ascertain the diagnosis. Among the most common traits are:




Low muscle tone
A single deep crease across the center of the palm
small skin folds (Epicanthal folds) on the inner corner of the eyes
Enlargement of tongue in relationship to size of mouth
C. GENETIC COUNSELING FOR PARENTS WITH A DOWN SYNDROME CHILD
Giving the diagnosis of Down syndrome to a couple, either antenatally or in the immediate after
birth, requires all of the doctor's communication and counselling skills.
Q. Imagine you are a doctor who has just made a confirmed diagnosis of Down syndrome in a mother at
the 20 weeks of gestation.
What advice would you give to the couple?
D. DOWN SYNDROME'S SOCIOLOGY
Advocates for people with Down Syndrome stress that they have the same
human rights, emotions,
dignity and value as any other human being. The abuse and forcible institutionalization of
people with Down syndrome was closely linked to early twentieth-century racial and eugenic theory,
culminating in the murder of many people with Down syndrome and other disabilities by the Nazi
government in Germany in the 1930s-1945, and the creation of compulsory sterilization
programs around the world which targeted the mentally disabled. Today, Down Syndrome is considered a ground
for
abortion in an increasing number of countries.
E. FAQS:
1. Can Down syndrome be inherited?
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Health and diseases_non-communicable diseases_genetic diseases P.16
Most cases of Down syndrome are not inherited, but occur as random events during the formation
of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in
reproductive cells with an abnormal number of chromosomes.
Mosaic Down syndrome is also not inherited. It occurs as a random error during cell
division early in fetal development. As a result, some of the body’s cells have the usual two copies of
chromosome 21, and other cells have three copies of the chromosome.
Translocation Down syndrome can be inherited. An unaffected person can carry a
rearrangement of genetic material between chromosome 21 and another chromosome. This rearrangement is
called a balanced translocation because there is no extra material from chromosome 21. Although they do not
have signs of Down syndrome, people who carry this type of balanced translocation are at
an increased
risk of having children with the condition.
2. Is it true that adults with Down syndrome are unable to form close
interpersonal relationships leading to marriage.
False: People with Down syndrome date, socialize and form ongoing relationships. Some are beginning to
marry. Women with Down syndrome can and do have children, but there is a 50 percent chance
that their child will have Down syndrome. Men with Down syndrome are believed to be sterile, with only one
documented instance of a male with Down syndrome who has fathered a child.
Q. Draw diagrams to show how non-disjunction followed by fertilization can result in Down syndrome
End