Download Document

Trial Version
Case Study: Common genetic diseases in Hong Kong
Key Concepts:
 Common genetic diseases in Hong Kong
 Causes of genetic diseases
 Common childhood genetic disorders in Hong Kong
 Common adult-onset genetic disorders in Hong Kong
 Ways to prevent genetic diseases
 Treatments for haematopoietic genetic diseases
 Ethical, legal, and social implications

Prior to this class, students are asked to search “news article” relating to the
common genetic diseases in Hong Kong.

Divide students into groups of 3 to 4 per group. Each group is required to prepare
the following before class:
1.
2.
3.
4.
5.
6.
7.
8.
9.

Discuss what a genetic disorder is and how it is passed down from generation
to generation.
What are the causes of genetic disorders? Mutation, radiation, etc
Are certain people more likely to suffer from genetic disorders? Example: older
mothers.
What are the common childhood genetic diseases in HK?
What are the common adult-onset genetic diseases in HK?
How to prevent genetic diseases?
Are there any treatments for genetic diseases?
If you think people should seek genetic counseling before they have children.
Explain why you think so.
If an expectant parent knows that their unborn child has a genetic disorder what
options do they have and what do you think they should do? Include ideas such
as genetic engineering performed before and after birth. Discuss your
suggestions.
Prepare notes and questions to be discussed before the session:
Level of Difficulties:
[1] Prior concepts.
[2] Essential concepts.
[3] Big and global concepts.
1
Trial Version
Notes about Genetic Disorders
1.
What are genetic disorders? [1]
Both genetic and environmental factors play pivotal roles in the development of a
disease. In general, a genetic disorder refers to “a disease caused by abnormalities
in an individual’s genetic material (genome).” Such abnormalities can be resulted
from parental inheritance leading to childhood genetic diseases, or from over-time
interaction with the environment contributing to accumulated genetic changes in
patients with adult-onset genetic diseases.
Human beings have 46 human chromosomes, including 22 pairs of autosomal
chromosomes and 2 sex chromosomes (XX or XY). Among them, there are
almost 3 billion DNA base pairs that code for about 30,000 to 40,000 proteins
(one gene codes for one protein). In fact, some genetic disorders are the direct
result of single mutation in one gene. However, in cases such as diabetes, asthma,
cancer, and mental illnesses, it is likely that more than one mutation is required
before the genetic disorder is manifest, and numerous genes may work together to
make contribution to a person's susceptibility.
2.
What are the causes of genetic disorders? [2,3]
Four causes of genetic disorders:
a.
Single-gene (also called Mendelian or monogenic) mutation:

This type is caused by mutation(s) in the DNA sequence of one gene. When
a gene is altered its protein product can no longer carry out normal
functions. There are more than 6,000 known single-gene disorders, which
occur in about 1 out of 200 births. Single-gene disorders are inherited in
patterns - autosomal dominant, autosomal recessive, and X-linked.
Autosomal dominant: A single, abnormal gene on one of the autosomal
chromosomes (one of the 22 "non-sex" chromosomes) from either parent
can cause certain diseases. One of the parents will usually have the disease
since it is dominantAutosomal recessive: An abnormal gene on one of the
autosomal chromosomes (one of the 22 "non-sex" chromosomes) from each
parent is required to cause the disease. People with only one abnormal gene
in the gene pair are called carriers, but since the gene is recessive they do not
exhibit the disease.

Sex-linked dominan: A single abnormal gene on the X chromosome can
cause the disease. The disease is likely to be transmitted to boys and girls.
Boys have a higher chance to get the disease since boys have one X
chromosome.
 Reference: Genetic Interest Group –
(http://www.gig.org.uk/education2.htm)
2
Trial Version
Examples of genetic diseases in this group are:
i.
Sickle cell anemia - Sickle cell anemia is an autosomal recessive genetic
disorder and its mutation reflects a single change in the amino acid building
blocks of the oxygen-transport protein, hemoglobin. Sickle cell anemia is a
hereditary form of anemia in which the red blood cells become sickleshaped (shaped like a crescent) and less able to carry oxygen. The presence
of two defective genes is needed for sickle cell anemia. If each parent carries
one sickle hemoglobin gene and one normal gene, each child has a 25%
chance of inheriting two defective genes and having sickle cell anemia; a
25% chance of inheriting two normal genes and not having the disease; and
a 50% chance of being an unaffected carrier like the parents.
(Reference: How does sickle cell cause disease? http://sickle.bwh.harvard.edu/scd_background.html)
Huntington’s disease – Hungtington’s disease (HD) occurs as a single,
autosomal, dominant gene. Because it is not a sex-linked condition, men and
women share an equal risk of inheriting the disease. HD is a fatal,
neurological illness causing involuntary movements, severe emotional
disturbance and cognitive decline. Huntington's disease usually strikes in
mid-life, in the thirties or forties, although it can also attack children and the
elderly. There is no treatment to stop the progression, which leads to death
after ten to twenty-five years. HD’s dominance presents a serious threat to
future progeny; offspring of an HD parent stand a 50 percent chance of
receiving HD.
ii.
Cystic fibrosis (CF) – CF is a genetic disease of the exocrine glands,
usually developing during early childhood and affecting mainly the
respiratory system, pancreas and sweat glands. It is characterized by the
production of abnormally viscous mucus by the affected glands, usually
resulting in chronic respiratory infections and impaired pancreatic functions.
In CF, each parent carries one abnormal CF gene and one normal CF gene
but shows no evidence of the disease because the normal CF gene dominates
or "recesses" the abnormal CF gene. To have CF, a child must inherit two
abnormal genes - one from each parent. The recessive CF gene can occur in
both boys and girls because it is located on non-sex-linked chromosomes
called autosomal chromosomes. CF is therefore called an autosomal
recessive genetic disease. The inheritance patterns for the CF gene are
shown in the accompanying diagram. Each child, whether male or female,
has a 25 percent risk of inheriting a defective gene from each parent and of
having CF. A child born to two CF patients (an unlikely event) would be at a
100 percent risk of developing CF.
(Reference: Learning about Cystic fibrosis –
(http://www.genome.gov/10001213)
3
Trial Version
iii.
Marfan syndrome – Marfan syndrome is a hereditary disorder principally
affecting the connective tissues of the body, manifested in varying degrees
by excessive bone elongation and joint flexibility and by abnormalities of
the eye and cardiovascular system. Marfan syndrome is a single abnormal
gene located on chromosome 15 and containing the coding for fibrilin, a
connective tissue protein, which is responsible for Marfan syndrome. Most
of the time this gene is inherited as an "autosomal dominant" condition from
a parent who is affected. About 30% of cases occur when the abnormal gene
arises in an egg or a sperm of an unaffected parent. Each child of a Marfan
sufferer has a 50-50 chance of inheriting the syndrome.
(Reference: Marfan’s syndrome http://www.dundee.ac.uk/medther/tayendoweb/images/marfan.htm)
iv.
Hereditary hemochromatosis – Hemochromatosis is a hereditary disease
characterized by improper processing by the body of dietary iron which
causes iron to accumulate in a number of body tissues, eventually causing
organ dysfunction. It is the main iron overload disorder. Hereditary
hemochromatosis is an autosomal recessive disorder of iron metabolism
with a gene frequency of 1/10 people of Northern European origin. The
homozygote frequency is 1/200 to 1/400, making it one of the most common
genetic disorders known.
(Reference: Hemochromatosis - http://www.diabetes.org/type-1diabetes/hemochromatosis.jsp)
b.
Multifactorial (also called complex or polygenic) mutation:
This type is caused by a combination of environmental factors and mutations
in multiple genes. For example, genes that contribute to breast cancer
susceptibility have been attributed to abnormalities on chromosomes 6, 11,
13, 14, 15, 17, and 22. Other examples of genetic disorders in this group
include Alzheimer’s disease, cancer, heart disease, high blood pressure,
arthritis, diabetes, and obesity.
c.
Chromosomal abnormalities:
Chromosomes, made up of DNA and protein, are located in the nucleus of
each cell. Since they are carriers of genetic material, abnormalities in
chromosomal structure such as missing copies, extra copies, translocation
(DNA from one chromosome breaks off and becomes attached to a different
chromosome), deletions (the loss of part of a chromosome), or inversions
(the rearrangement of the DNA in part of a chromosome) can result in
disease. Down syndrome, or trisomy 21, is a common genetic disorder with
chromosomal abnormality. All Down syndrome patients have three copies of
chromosome 21.
4
Trial Version
d.
Mitochondrial abnormalities:
Mitochondria are small rod-like organelles that are involved in cellular
respiration for the production of energy. Each mitochondrion may contain 5
to 10 circular pieces of DNA. This comparatively rare type of genetic
disorders is caused by mutations in the DNA inside mitochondria.
Mitochondrial myopathy (A group of neuromuscular diseases caused by
damage to the mitochondria), encephalopathy (Encephalopathy is a term for
various conditions affecting the brain. Generally, it affects large parts of the
brain (or the whole organ), instead of leading to identifiable focal changes.),
lactic acidosis and stroke-like episodes (MELAS) are the most common
maternally inherited genetic disorders with mitochondria.
Reference:
 Genetic Disorder Corner – (http://gslc.genetics.utah.edu/units/disorders/)
 Gene Therapy Solution – (http://www.genesolutions.com/index.html)
3.
What are the common childhood genetic diseases in Hong Kong?[2]
The three common childhood genetic diseases in Hong Kong are:
a)
Thalassemia (α and β)
Thalassemia is an inherited disease of the red blood cells. The genetic defect
results in synthesis of an abnormal hemoglobin molecule. The blood cells
are vulnerable to mechanical injury and die easily. To survive, many people
with thalassaemia need blood transfusions at regular intervals. Thalassemia
α and thalassemia β are resulted from defects in α or β hemoglobin chain
respectively, giving rise to anemia. The disease results in decreased and
defective production of hemoglobin (a molecule found inside all red blood
cells) necessary to transport oxygen throughout the body. In Hong Kong, the
incidence of various forms of thalassemia α is 4.5%, whereas thalassemia β
affects 3-6% of the local population.
b)
Hemophilias A and B
Hemophilia is a congenital (hereditary) disease which lacks of a blood
clotting factor that prevents a person's blood from clotting properly;
therefore patients with hemophilia have a tendency to bleed excessively. For
normal people, clotting factors mix with blood platelets to form fibers,
which make the clot stronger and stop the bleeding. Our bodies have 12
clotting factors, numbered from I through XII. Having deficiency in clotting
factors VIII and IX is what causes hemophilias A and B, respectively.
Hemophilia is an X-linked disorder that affects mostly boys (because boys
have only one X chromosome). In Hong Kong, hemophilia A affects 1: 10
000 live-born males, whereas the incidence of hemophilia B is just about
half that of hemophilia A.
5
Trial Version
c)
4.
Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is caused by mutation of a gene
located on the short arm of X chromosome that makes a protein called
dystrophin. This protein helps muscle cells keep their shape and provide
strength. The X-linked recessive disorder affects 1:3500 live-born males in
Hong Kong. DMD patients usually present muscular weakness in early
childhood. By age 10 or 12, children with DMD often need to use a
wheelchair. In addition, their heart and lungs may also be affected, and
DMD patients mostly die from respiratory failure in their third decade of
life.
What are the common adult-onset genetic diseases in Hong Kong? [2]
The two most common adult-onset genetic diseases in Hong Kong are:
a)
Huntington’s disease
Huntington’s disease (HD) is a neurodegenerative autosomal dominant
disorder that manifests in mid-life. HD patients present dementia, cognitive
and psychiatric impairments. Disease progression to death usually occurs 10
to 15 years following onset of the disease.
b)
Alzheimer’s disease
Alzheimer’s disease (AD) is the commonest form of dementia. Apart from
dementia, patients usually present cognitive impairment including
absentmindedness and poor comprehension of languages. The cause for its
progressive deteriorating course is still mysterious. The age of onset in most
cases is over 60. In a study reported by the Queen Mary Hospital the mean
age was 77 years old.
5.
How to prevent genetic diseases? [2,3]
In order to prevent childhood as well as adult-onset genetic disorders, premarital
counseling, prenatal diagnosis, newborn screening, and pre-symptomatic testing
for predicting adult-onset disorders have been employed in Hong Kong. For some
X-linked genetic diseases, females are usually only carriers of the disease.
Therefore, carrier testing and prenatal diagnosis are offered to those with a
positive family history.
a)
Public education, counseling and more widespread screening programme to
detect couples at risk:
Since 1990, screening has been extending to couples attending the Family
Planning Association clinics (FPA) in Hong Kong for premarital counseling.
If both partners are found to have the same type of thalassemia trait, they are
counseled according to the mode of inheritance and management of the
congenital disorders.
6
Trial Version
b)
Prenatal diagnosis programme:
To date, prenatal testing for and thalassemia has been established since
1982 with around 100 cases of thalassemia and 50 cases of thalassemia
annually. Since 1997, non-invasive ultrasound diagnosis of fetus is also used
to diagnose and thalassemia. In addition, with the isolation of the DMD
gene in 1987, prenatal diagnosis and carrier testing for DMD has become
widely available in Hong Kong.
c)
Newborn screening
For inherited metabolic diseases in Hong Kong, most patients are diagnosed
at the neonatal, infantile, or childhood stage of development. For example,
there are territory wide screening programme for congenital hypothyroidism
and glucose-6-phosphate (G6P) dehydrogenase deficiency in Hong Kong
since 1984.
d)
Pre-symptomatic testing for predicting adult-onset disorders
Pre-symptomatic testing of at-risk individuals is regarded as welcome
preventive measures to stop passage of Huntington’s disease and
Alzheimer’s disease to future generations. (Discuss with your students
whether such tests are desirable. Knowing one is prone to these diseases
would put much stress on a person and highly affect his/her quality of life.
Also, insurance companies may reject these patients to buy, say life
insurance. Do you think this is fair?)
6.
What are the treatments for haematopoietic diseases? [2, 3]
a)
Haemopoietic stem cell transplant (HSCT)
Haemopoietic stem cell transplant (HSCT) has been available at two
hospitals in Hong Kong since 1991. HSCT is employed to treat patients with
genetic blood disorders such as thalassemia (α and β). For stem cell
transplant (SCT), stems cells are collected from the bone marrow (known as
bone marrow transplantation, BMT) or from the bloodstream (known as
peripheral blood SCT) of patient’s blood-matched siblings. At the Prince of
Wales Hospital, in 44 BMT cases there were five treatment-related
mortalities and two rejections. The overall disease free survival was 84%. At
Queen Mary Hospital, in 18 cases the overall disease free survival at 5 years
was 61%. The recent use of cord blood SCT from compatible siblings,
identified through the prenatal diagnosis program, had a 100% favorable
transplant outcome. (Please refer to the “Stem cells and their applications for
more information.)
7
Trial Version
Down sides:
In fact, such clinical procedures are very expensive and tricky in searching
for suitable blood-matched donors for patients receiving HSCT. Moreover,
life-threatening graft-versus-host disease (GVDH) still represents a major
complication of HSCT, which occurs when the immunocompetent donor
white blood cells contained in the graft attack patient’s epithelial surfaces of
the skin and mucous membranes, biliary ducts of the liver, and crypts of the
intestinal tract, as a result of blood cell disparities between the donor and the
immunosuppressed patient. The most disabling symptoms of GVHD are
severe skin rashes and severe diarrhea.
b)
Life-long transfusion- chelation therapy
Patients presenting anemia resulted from thalassemia or sickle cell anemia
are given the transfusion and iron-chelation therapy. The homozygous
thalassemia child usually presents anemia by 6-9 months of age. A hightransfusion regime is used to maintain the child at normal haemoglobin
concentration. This is most likely at 6 weekly intervals. In addition,
chelation therapy* with iron-chelating agent (e.g. dexferroxamine in Hong
Kong) is given to remove excess iron after 12 to 18 months of starting
regular blood transfusion regime. Patients are taught to use the infusion
pump and to administer the drug.
Down sides:
In many instances, the chelation therapy does not fully chelate all excess
iron. Furthermore, patients need to have daily infusion for 5 days per week.
They would have difficulties in obtaining employment due the daily
infusions.
*Why iron-chelation therapy can treat thalaseemia or sickle cell anemia?
Because the body naturally eliminates iron at a very slow rate, excess iron levels
will remain essentially undiminished unless chelation therapy is provided. It
takes years of therapy to reduce the total body storage iron of patients who are
severely overloaded to normal levels. The benefits of iron chelation therapy are,
however, usually clinically apparent within a much shorter timeframe. This
observation has led some to suggest that the benefits of iron chelation therapy
may in large measure result from its ability to effectively detoxify iron by
removing it from the labile iron pool. The clinical utility of iron chelation
therapy may thus result more from its effect on iron toxicity rather than iron.
8
Trial Version
7.
What are some of the ethical, legal, and social implications of being diagnosed
with a genetic disease? [2,3]
Since most of the genetic disorders are incurable and may need life-long
management, testing and results should be requested by and made available only
to the concerned individuals with adequate counseling. For patients, such results
become part of their medical record, insurance companies, employers, and other
agencies should not be able to access the information. Therefore, legal measures
should be enacted to protect patients from misuse of their medical record. Patients
with certain genetic disorders are potentially denied from insurance coverage,
employment, or other benefits. Additionally, prenatal diagnosis may sometimes
result in abortion. Termination of an affected pregnancy may lead to
psychological disturbances to the mothers. Therefore, professional counseling
with medical personnel is very important to give information, answer questions,
and offer support to persons and families.
We should all aware the followings:
1.
Are patients being properly informed about the risks and limitations of
genetic technology?
2.
How does personal genetic information affect an individual in our society?
3.
Who has right to own genetic information?
References:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Your Genes, Your Health – (http://www.ygyh.org/)
Making a Karyotype (http://gslc.genetics.utah.edu/units/disorders/karyotype/karyotype.cfm)
Gene and Diseases http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.p
reface.91
Genetic Disorder information on the net –
(http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/disea
seindex.shtml#general)
How genetic disease occur –
(http://www.mydna.com/genes/genetics/genetics101/geneticdisorders_family.html
Thalassemias in Hong Kong – (http://www.cchi.com.hk/specialtopic/case2/)
Thalassemias – (http://kidshealth.org/parent/medical/heart/thalassemias.html)
Hemophilia –
(http://www.kidshealth.org/teen/diseases_conditions/blood/hemophilia.html)
Prenatal diagnosis of common single gene disorders by DNA technology –
(http://sunzi1.lib.hku.hk/hkjo/view/22/2200278.pdf)
Muscular Dystrophy –
(http://www.kidshealth.org/teen/diseases_conditions/bones/muscular_dystrophy.htm
l)
Risk factors of institutionalization among AD patients –
(http://www.hkgs.org.hk/JHKGS0401p007.pdf)
Thalassemia – (http://www.cchi.com.hk/abs_reviews/thalassemia/thalassemia1.htm)
Sickle cells – (http://www.scinfo.org/neurosx.htm)
Gene Test –
(http://www.genetests.org/servlet/access?id=8888891&key=ql42gDHPrhNfN&fcn=
y&fw=sBjk&filename=/concepts/conceptsindex.html)
9
Trial Version
Local news [3]
Keywords
遺傳性疾病
Title
Newspaper
青年人中風與法布裡病有關
時刻警惕大腸癌
髓鞘病
表證難成痛卻纏身
女護士被鬧鐘驚嚇猝死
生男生女該有選擇嗎？
殺生抑救人爭議不休
泰地中海貧血症嬰兒增加
病童內出血隨時奪命
新療法編輯基因治遺傳病
基因療法突破可改子女特徵 剪輯基因可望治愛滋
遺傳病千奇百怪港現侏儒嬰
大公報
都市日報
信報財經新聞
新報
新報
太陽報
東方日報
香港商報
太陽報
蘋果日報
明報
太陽報
Page number
中華醫藥 C04
焦點 P20-P21
副刊專欄 P35
風月廊 E03
放眼世界 A10
社會及專欄 A27
國際 A15
醫藥保健 B06
本地新聞 A02
國際要聞 A17
國際要聞 A16
每日專題 A34
Date
2005-08-15
2005-07-05
2005-06-29
2005-06-24
2005-06-01
2005-05-31
2005-05-26
2005-05-15
2005-04-12
2005-04-05
2005-04-05
2005-03-25
Glossary
English
Chinese
Alzheimer's Disease
Autosomal
Chromosome
Cystic fibrosis
Dominant
Duchenne muscular dystrophy
Genetic disease
Genome
Graft-versus-host disease
Haemopoietic Stem Cell
Hemophilias
Huntington’s disease
Inheritance
Iron-chelation therapy
Mendelian
Monogenic
Muscular Dystrophy
Mutation
Recessive
Sickle cell anaemia
Thalassemias
老年癡呆症
正染色體的
染色體
囊胞性纖維症
(遺傳性狀)優勢的
裘馨氏肌肉萎縮症
遺傳性疾病
基因組
移植物抗宿主病
血幹細胞移植
血友症
亨丁頓舞蹈症
遺傳
鐵螯合劑
孟德爾遺傳定律的
單基因的
肌肉萎缩症
變種
(遺傳性狀隱性的
鐮狀細胞性貧血
地中海型貧血
10