Chapter 11 Contd.AS SUPPLIMENT

Gaucher Disease Huntington’s Disease Hemophilia Parkinson’s Disease Phenylketonuria Sickle Cell Anemia Cystic Fibrosis Down Syndrome Alzheimer’s Disease SCID: Severe Combine Immunodeficiency Type I Diabetes Achondroplasa Autism Others

1. Single Gene: 1. Single Gene: › Disorders caused by abnormality or mutation in the sequence of one gene

2. Multifactorial:2. Multifactorial:› caused by a combination of environmental as well as mutations in

multiple genes

3. Chromosomal:3. Chromosomal:› Abnormalities in chromosome structure such as missing or extra copies

4. Mitochondrial:4. Mitochondrial:› caused by a mutation in the non chromosomal DNA of the

mitochondria.

Gaucher disease is a genetic disorder handed down from generation to generation. It is the most common of the lipid storage diseases. It is caused by deficiency of the enzyme, β-glucocerebrosidase.

When there is not enough of the enzyme, the fat can

not be broken down and is stored primarily in the liver and spleen

Other body tissues, bones and organs may also be affected. In rare cases, it may also accumulate in the brain.

bone pain and fractures

easy bruising fatigue seizures Liver and spleen

enlargement

In the past the only potential treatment was removal of the spleen (splenectomy).

This has given way to injections of a replacement synthetic enzyme (Cerezyme/Ceredase).

Gene therapy is an experimental approach.

A novel oral treatment has recently been evaluated. This drug is known as N-butyldeoxynojirimycin (OGT 918).

The mechanism of action is by inhibiting the formation of glucocerebroside.

Huntington’s Disease results from genetically programmed degeneration of nerve cells in certain areas of the brain.

This degeneration causes uncontrolled movements, loss of intellectual faculties, and emotional disturbance.

Early signs of Huntington’s disease include mood swings and irritability, depression, loss of memory, and uncontrolled movements.

As the disease progresses, walking and speech become more difficult, and memory and intellectual functions continue to decline.

Hemophilia is the oldest known bleeding disorder. It is a sex-linked disorder, which is why it appears

mostly in males. Hemophilia is like any other sex-linked disorder,

because the “hemophilia” gene is on the X chromosome.

2 types of Hemophilia:› Hemophilia A: Lack the blood clotting protein

factor VIII› Hemophilia B: Lack the blood clotting protein

factor IX.

Clotting factors: Given in differing doses according to the weight of the individual and the severity of the bleeding.

Recombinant DNA Techniques: Clotting factor genes are grown synthetically.

Clotting factor products from human blood plasma are not used due to chances of being contaminated with viruses such as HIV or Hepatitis.

Gene Therapy› A major focus of research in hemophilia centers.› Because only one defective gene is involved,

replacing that gene effectively may cure hemophilia.

› Although gene therapy may eventually replace treatment for individuals with hemophilia, it will not eliminate defective genes in carriers, who could still pass hemophilia to their children.

› Currently studies are being conducted for type B hemophilia to determine the safety of the gene transfers.

Parkinson’ s disease is a neurological condition that has a genetic component next to Alzheimer’s.

The chance of getting or developing Parkinson’s gets higher as age increases.

DOPAMINE Chemical produced in the middle part of the brain that is responsible for organizing coordinated movements and to send this signal to the control centers of the brain.

•In Parkinson’s disease, this chemical is not produced enough and functioning starts to shut down slowly & patient begins to lose control over many vital voluntary movements from swallowing to walking.

SYMPTOMS Some symptoms include hand tremor, muscle spasms, rigidity, lack of postural stability, memory loss, blurriness, drooling, and difficulty in voluntary movements.

•Michael J. Fox Foundation.

•National Parkinson Foundation.

•Nearly $70 million in research programs funded

•Rare metabolic autosomal recessive disorder

•Affects protein breakdown in the liver resulting in mental retardation & genetic Mutation occurs on Chromosome 12

•The mutated gene is supposed to code for a protein which produces phenylalanine hydroxylase

•Without phenylalanine hydroxylase, phenylalanine (found in protein rich foods) cannot be converted to tyrosine

•Excess phenylalanine in the body will result in mass production of phenylpyruvic acid

•Phenylpyruvic acid cannot be absorbed by the kidney and thus excess phenylalanine and phenylpyruvic acid enters cerebrospinal fluid and then the brain causing severe mental retardation.

Downloaded from: StudentConsult (on 10 February 2006 10:40 PM)

Unable to metabolize phenylalanine

If Untreated in Infants:

•Severe brain damage

•Epilepsy

•Behavioral Problems

•Stunted growth

•Symptoms Throughout Life if Treatment is not Followed Closely:

•Musty body odor

•Increased muscle tone

•Fair skin and eyes

•Vomiting & Active muscle tendon reflexes

•Due to the large amount of research done in Phenylketonuria patients can live a normal life while adhering to a strict protein-free diet

•Research is still being done to determine if there is a better biochemical model for the effects of PKU on the body

•If more detailed biochemical pathways of the effects of PKU can be determined there may be a method of introducing necessary chemical properties into the body, preventing some of the long term effects of PKU.

Fatigue Pain Crisis Dactylitis and Arthritis Bacterial Infections Splenic Sequestration Lung and Heart Damage Leg Ulcers Aseptic Necrosis and Bone Infarcts Eye Damage Jaundice Acute Chest Syndrome

Treatments› Antibiotics› Pain-relieving Medications› Supplemental Oxygen› Blood Transfusions› Health maintenance starts with early

diagnosis

An inherited disease that affects sodium channels in the body and causes respiratory and digestive problems.

There is no cure for Cystic Fibrosis and treatment can slow progression of the disease

One in 25 people carry the gene but will have no symptoms

CF is usually diagnosed at birth CF is not contagious CF occurs in males and females.

Excessive production of thick, sticky mucus in the airways

Affects tissues in the airway, gastrointestinal tract, ducts of the pancreas, the bile ducts of the liver, and the male urogenital tract

Causes difficultly clearing infections and can result in lung damage over a period of time.

Persistent cough, with great physical effort Some difficulty breathing Tiredness, lethargy or an impaired exercise ability Frequent visits to the toilet Salt loss in hot weather which may produce muscle

cramps or weakness Poor appetite.

Caused by genetic mutation in a single gene on chromosome 7

Gene contains building info for CFTR

Mutation causes a CFTR that won’t open.

Chest physiotherapy Antibiotics Inhalations via a compressed air pump and

nebuliser Enzyme replacement capsules with meals and

snacks A well balanced diet high in protein, fat and

kilojoules Supplementary vitamins Salt supplements Regular exercise.

Down syndrome is caused by an extra chromosome present on chromosome 21

› Down syndrome is caused by mutations

› Forms of Down syndrome Klinefelter’s disease Turner’s syndrome Philadelphia chromosome

› A genetic form of Down syndrome: Mosaicism

Alzheimers is a form of dementia that causes changes in the brain, and affects a person’s memory, mood, and behavior.

Disease mostly affects people over 65. Diagnosis:

› There is no specific test for Alzheimer’s disease, however, physician are able to look at a person’s medical history, do a complete physical or give a memory and/or psycological test to see how well the brain works.

› Brain scan.

Diseased Diseased Pancreatic TissuePancreatic Tissue

Severe disorder from an array of the Autism Spectrum Disorders (ASD)

Another common form of ASD is Asperger Syndrome

Developmental disorder affects parts of brain, notably the amagdala, hippocampus, and cerebellum› immune system, and gastrointestinal tract

1 out of 150 people are affected More prevalent in males than in females.

difficulties with social interaction

problems with verbal and nonverbal communication

repetitive behaviors or narrow, obsessive interests

behaviors can range in impact from mild to disabling.

Complex,polygenic and multifactoral› Highly heritable› Gene-environment

interaction

Vaccines.

Changes in longevity Changes in availability of Changes in availability of resourcesresources

Changes in transits Changes in climateChanges in climate

Stem Cells

Gene Therapies

Advanced IVF Techniques

Therapeutic Cloning

•Stem cell collected from adult can be harvested from many area

including the bone marrow.

•Alternative to Embryonic Stem cells

•Potential to reverse and cure Diabetes

•Use undifferentiated cell from embryos and cultures them to

grow into need cells

•Many ethical and social concerns surrounding this research

•Neurons Grown from Embryonic Stem Cells Restore Function in

Paralyzed Rats

•Hold potential cures for 1000s of diseases many genetic disorders.

•This treatment is aimed at women who would pass on a genetic defect to the child.

•Also helps women who suffer with mitochondria disease.

•Faulty genes are removed from the embryo , and replaced by

healthy genes from the additional woman.

•Using stem cells to replace or create tissues and organs

•Currently heart tissues and full bladders are being grow

in lab

Fig. Stem cell treatments and tissues recreated in the

heart of a child

There are four types of Genetic Disorders:Single gene, Multifactorial, Chromosomal, Mitochondria Heredity plays a big role in GD Phenotype is genes being express as characteristic Genotype is all the gene present in the genome Evolution needs mutations to adapt organism which is essential for

survival GD are mutations that had some kind “fitness” for the organism and get

promoted to the next generation. GD are apart of our adaptations to environments, but as the world changes

rapidly GD become added problems in a complex world. Scientists are working on treatment that can cure, reverse, prevent and

remove GD from individual. GD will always be apart of our species but the future hold promising way

to suppress the damaging effects of GD.

National Institute of Diabetes, Digestive, and Kidney Diseases, NIH Publication No. 97-4200, July 1997, e-text posted: 12 Feb 1998.

Baz R, Mekhail T. Clotting Factor Deficiencies. The Cleveland Clinic. Reviewed July 15, 2004. Available at: https://www.clevelandclinicmeded.com/diseasemanagement/hematology/ clotting/clotting.htm. Accessed April 1, 2006.

Bicker B, Kwiatkowski JL. Coagulation disorders. In: Dipiro JT, Talbert RL, Yee GC, et al. (eds.). Pharmacotherapy: a Pathophysiologic Approach. 5th ed. New York: McGraw Hill; 2002.

Griffin M.D., Gregory C. Hemophilia. Teens Health, Nemours Foundation. Available at: http://kidshealth.org/teen/diseases_conditions/blood/hemophilia.html. Accessed April 4, 2006.

Peter Turnpenny, Sian Ellard. Emery’s Elements of Medical Genetics, textbook 12th Edition, Chapter 11

Dr. Estella Chen. Lecture notes from Medical Genetics. Located on WebCT based on Metabolic Disorders

“Living with PKU”, Published by Inherited Metabolic Disease Clinic, University of Colorado. http://www.medhelp.org/lib/pku.htm

Phenylketonuria. Genetic Science Learning Center, University of Utah, 2006. http://gslc.genetics.utah.edu/units/disorders/whataregd/pku/index.cfm

The Genetic Disease Phenylketonuria. Melissa G. Price, Department of Biology, Missouri State Western University 2006. http://clearinghouse.missouriwestern.edu/manuscripts/159.asp

The History of Newborn Phenylketonuria Screening in the U.S.. Diane B. Paul, University of Massachusetts. The Medical and Public Health Law Site. file:///E:/pku%20screening%20history.htm

Bowman-Kruhm, Mary. Everything You Need to Know About Down Syndrome. New York: Rosen Publishing Group, 2000.

Edelson, Edward. Genetics and Heredity. New York: Chelsea House Publishers, 1990.

Tocci, Salvatore. Down Syndrome. Danbury: Grolier Publishing, 2000.

……………………………. Lieberman, Abraham. “ The New Genetics of Parkinson Disease: Is Parkinson Disease Inherited?” National Parkinson Foundation. April 08, 2006.

http://www.parkinson.org/site/apps/s/content.asp?c=9dJFJLPwB&b=108269&ct=89702 . “Parkinson Primer”. National Parkinson Foundation. April 1, 2006. http://www.parkinson.org/site/pp.asp?c=9dJFJLPwB&b=71354. “Parkinson Overview.” Health A to Z. April 1, 2006. http://www.healthatoz.com/healthatoz/Atoz/dc/caz/neur/park/parkwhat.jsp. “Specific Genetic Disorders.” National Human Genome Research Institute. March 28, 2006. http://www.genome.gov/10001204. “Two types of Parkinson’s”. BBC News. March 28, 2006. http://news.bbc.co.uk/1/hi/health/263798.stm. “Types of Parkinson’s Diseases”. Mayo Clinic. April 1, 2006. http://www.mayoclinic.org/parkinsons-disease/types.html. “What are Genetic Disorders?”. Genetic Science Learning Center. April 1, 2006. http://gslc.genetics.utah.edu/units/disorders/whataregd/ Brooker, Robert. Genetics: Analysis and Princeples; McGraw-Hill

Higher Education: Columbus, OH, 2005. Campbell, Neil A. Biology: Sixth Edition; Pearson Education Inc.: San

Francisco, CA, 2002. Charache, S. et al. “Effects of Hydroxyurea on the Frequency of Painful

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