Genetic Disorders: April 2012

Thursday, April 26, 2012

Phenylketonuria

This genetic disorder is also abbreviated as PKU.

This disorder usually manifests itself in infants through mental retardation and behavioral problems. There is also the potential for seizures, developmental delay, and autism.

This disorder can either be inherited or found in gene mutations. Specifically, mutations in the PAH gene cause low levels of “an enzyme called phenylalanine hydroxylase” (“Phenylketonuria” 1). This enzyme causes a person to be unable to digest phenylalanine.

PKU is treated by “limiting the amount of protein in the diet. Treatment also includes eating low-protein foods and taking vitamins and minerals” (“Phenylketonuria” 1).

PKU is typically tested for through a newborn screening test that is done shortly after birth through a blood sample.

This disorder manifests itself typically in myopia which is nearsightedness. There is also an increased risk for retinal detachment, glaucoma and early cataract formation. Additionally, there is also the potential for bone overgrowth and loose joints.

Marafan syndrome is caused by mutations in the FBN1 gene. This gene’s mutations are “associated with a broad continuum of physical features ranging from isolated features of Marfan syndrome to a severe and rapidly progressive form in newborns” (“Marfan” 1).

Marafan syndrome does not have a cure but there are many effective treatments available. Many of any of the symptoms are easily remedied. For example, the eye problems often can simply be fixed with glasses. Medication can also be used such as beta blockers to help protect the heart.

Individuals who have Marfan syndrome are advised to avoid contact and competitive sports because of their static nature (“Marfan” 1).

Symptoms of this genetic disorder include a characteristic facial appearance, short stature, heart defects present at birth, a broad or webbed neck and minor eye problems. Furthermore, there can also be bleeding problems, an unusual chest shape with widely spaced or low set nipples and developmental delay of varying degrees.

This syndrome is caused by changes in one of the autosomal dominant genes (“Noonan” 1). This disorder is caused at inception so a defective sperm or egg is a carrier for this disorder. Four genes, PTPN11, SOS1, RAF1 and KRAS, have been identified so far as being carriers for this disorder.

Treatment for Noonan syndrome is based upon the individual’s particular symptoms. Any symptoms are treated in the same way that they are treated for the normal population.

This disorder is present in about 1 in 1,000 to 1 in 2,500 people.

Gaucher Disease has no specific symptoms as it varies greatly among those who have the disorder. However, it is typically seen with an enlargement of the liver and spleen, a low number of red blood cells, easy bruising, and bone disease. There can also be defections within the heart, lung and nervous systems.

Gaucher disease is caused by mutations in the gene GBA. The mutations cause very low levels of glucocerebrosidase which is a normal part of the cell membrane. Essentially, this lipid that is part of the cell membrane will build up in the liver, spleen and bone marrow. This buildup interferes with normal functioning (“Gaucher” 1).

This is a very manageable genetic disorder. There is enzyme replacement therapy for the effective treatment for those who have this disorder. This treatment helps to reverse the symptoms of Gaucher disease. Other alternatives include oral treatments as well.

The only way to have this genetic disorder is if both of the parents have a mutated copy of the GBA gene originally (“Gaucher” 1).

Progeria is a genetic disorder that does not show itself until a child is about one year old. Within that year, the children are soon much shorter and weigh much less than others their age. These children also “develop a distinctive appearance characterized by baldness, aged-looking skin, a pinched nose, and a small face and jaw relative to head size” (“Progeria” 1). These children also have “symptoms typically seen in much older people such as stiffness of joints and hip dislocations” (“Progeria” 1).

Progeria is caused by a tiny, point mutation in a single gene called lamin A (LMNA). This gene codes for two proteins that “play a key role in stabilizing the inner membrance of the cell’s nucleus” (“Progeria” 1).

There is no possible treatment or cure for children with Progeria. This devastating condition will eventually kill the child around age 13. Unfortunately, this death is typically caused by a heart attack or stroke.

Progeria is derived from the Greek word meaning old age “geras” (“Progeria” 1).

Wednesday, April 25, 2012

Canavan Disease is often appreviated as CD.

Canavan Disease has multiple symptoms such as rapidly increasing head circumference, lack of head control, reduced visual responsiveness, and abnormal muscle tone (“What is” 1).

This disorder is a neurological disorder that affects the growth of the myelin sheath which is an insulator to protect nerves. Typically, a deficiency of the enzyme aspartoacylase is the main cause which causes a chemical imbalance destroying the myelin sheath.

There is no cure for this disease. Most often children with this disease do not even live past the age of 10. Most often, these children suffer seizures, become paralyzed and have trouble swallowing.

This disorder primarily affects children of eastern and central European Jewish descent (“What is” 1).

Angelman syndrome manifests itself through developmental delays. Most often, these delays include lack of crawling or babbling. Additionally, there can be a lack of or minimal speech, inability to walk, move or balance well, trembling movement of arms and legs, frequent smiling and laughter and a happy, excitable personality.

This disorder is most often caused by “problems with a gene located on chromosome 15 called the upiquitin-protein ligase E3A gene” (Staff 1). The problem is typically when chromosome 15 is missing or damaged. This chromosome is active in the brain.

There is no cure for this disease. Any treatment done helps manage the medical and developmental problems that the chromosome defects cause. Typically, this involves anti-seizure medications, physical therapy, communication therapy, and behavior therapy.

Typically people with this disorder do live a normal life span. However, as they age, these people may "become less excitable" (Staff 1).

Duchenne Muscular Dystrophy symptoms typically appear before age 6 (Board 1). These symptoms can include fatigue, mental retardation, muscle weakness, frequent falls, difficulty with motor skills and progressive difficulty of walking.

This genetic disorder is caused by a defective gene in a muscle protein called dystrophin. This disease is inheritable and most often affects males because of the way this disease is inherited.

There is no known cure for this disorder. Even treatment does not ensure any long-lived life. Most often, any treatment done is aimed at controlling symptoms in order to maximize the quality of life. Additionally, activity to help strengthen the muscles is encouraged.

This disease leads to quickly worsening disability. “Death usually occurs by age 23, typically from lung disorders” (Board 1).

People who have hemophilia typically have “prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases, heavy bleeding occurs after minor trauma or even in the absence of injury” (“Hemophilia” 1). Hemophilia is an inherited disease that is related to the X chromosome.

Hemophilia is caused by changes in the F8 gene and F9 gene. This gene contains the instructions to make the protein that is responsible for coagulation of blood. Coagulation of blood helps create blood clots which normally help to prevent further blood loss.

Hemophilia has no cure but can be managed through medications that help to promote blood clotting.

Hemophilia is more common in males than in females.

Crohn’s Disease

Abbreviated as IBD commonly in medical texts

Chrohn’s disease manifests itself through blockage of the intestine, sores and ulcers in the affected areas or surroundings tissues such as the bladder, tunnels around the anus and rectum called fistulas, nutritional deficiencies, anemia, arthritis, skin problems and many other symptoms.

Crohn’s disease is caused by “abnormal response by the body's immune system. The immune system is composed of various cells and proteins. Normally, these protect the body from infection. In people with Crohn's disease, however, the immune system reacts inappropriately. Researchers believe that the immune system mistakes microbes, such as bacteria that is normally found in the intestines, for foreign or invading substances, and launches an attack. In the process, the body sends white blood cells into the lining of the intestines, where they produce chronic inflammation. These cells then generate harmful products that ultimately lead to ulcerations and bowel injury. When this happens, the patient experiences the symptoms of IBD” (“About” 1).

Currently there is no treatment for Crohn’s disease. The best thing that can be done is regular medical monitoring and lessening of the symptoms through drugs, steroids, antibiotics and anti-diarrhea medications.

There is an inheritable risk for Crohn's disease especially "in families of Jewish ancestory" ("About" 1).

Friday, April 20, 2012

Down syndrome is also known as trisomy 21.

People who have down syndrome usually has physical abnormalities such as a flat face, a small broad nose, abnormally shaped ears, a large tongue and upward slanting eyes with small folds of skin in the corners.

Down syndrome is caused by nondisjunction of the pair of number 21 chromosomes. This means that these chromosomes “fail to separate during the formation of an egg (or sperm)… when the egg unites with a normal sperm to form an embryo, that embryo ends up with three copies of chromosome 21 instead of the normal two. The extra chromosome is then copied in every cell of the baby’s body” (“Down” 1).

There is no cure for Down syndrome. However, people can undergo physical therapy or speech therapy in order to help those with this disorder live a more normal life.

"Down syndrome is the most common genetic disorder caused by chromosomal abnormality. It affects 1 out of every 800 to 1,000 babies” (“Down” 1).

Turner syndrome typically affects growth and sexual development. Additionally, people affected by turner syndrome developed as girls. Girls with this disorder are “shorter than normal, and may fail to start puberty when they should. This is because the ovaries fail to develop properly. Women with Turner syndrome appear to have a stocky appearance, arms that turn out slightly at the elbow, a receding lower jaw, a short webbed neck and low hairline at the back of the neck” (“Turner” 1).

Turner syndrome is caused by a missing or incomplete X chromosome. Normally, females inherit one X chromosome from their mother and one X chromosome from their father. However, people with this disorder only have one X chromosome. This is caused by nondisjunction where “a pair of sex chromosomes fails to separate during the formation of an egg (or sperm). When an abnormal egg unites with a normal sperm to form an embryo, that embryo may end up missing one of the sex chromosomes… Because these girls only have one X chromosome, these girls are missing important genetic information which controls long bone growth and ovarian development.

This disorder is treated with hormone replacement therapy in order to reach normal height and also encourage normal hair and muscle growth. However, the specific types of hormones vary from androgens to estrogen depending on the desired result.

This syndrome affects 60,000 females in the United States.

Some of the symptoms of galactosemia include “kidney failure, an enlarged liver, cataracts, poor growth and mental retardation” (“Galactosemia” 1).

Galactosemia affects “the body’s ability to break down a food sugar called galactose” (“Galactosemia” 1). This food sugar is found in milk and other dairy products. These sugars are typically broken down by the body and used for energy. This disorder is passed down in an “autosomal recessive pattern. To get the disorder, a child must inherit one defective gene from each parent. Inheriting one normal gene and one mutated gene makes a person a carrier… Defects in galactose metabolism cause toxic chemicals to build up in cells of the body” (“Galactosemia” 1).

There is no cure for galactosemia. However a very effective treatment is monitoring what someone is eating and having dietary restrictions. Essentially, if someone with this disorder avoids foods and drinks containing galactose, including milk, cheese, and legumes, then the disorder does not manifest itself.

This disorder affects every 1 in 55,000 newborns.

Huntington’s Disease

Huntington’s Disease is often abbreviated as HD.

Huntington’s Disease “affects the part of the brain that controls thinking, emotion and movement. Most people who have the disease start to see symptoms between the ages of 30 and 50. Some symptoms include poor memory, depression, mood swings, lack of coordination, twitching, etc.” (“Huntington’s” 1).

Huntington’s Disease is inherited in an “autosomal dominant pattern. This means that everyone who inherits the faulty gene will eventually get the disease… HD is caused by a mutation in a gene on chromosome 4. The job of its protein product, huntingtin, is to direct the delivery of small packages to the outside of the cell. Normally the coding region of this gene contains the DNA sequence “CAG”… People with HD have an abnormally high number of the CAG triplets, approximately 40 or more (normal is 10 to 26 times)” (“Huntington’s” 1)

There is no cure for Huntington’s Disease. Even any treatments that have been found do not slow the progression of the disease. Instead, they help make the patient more comfortable. Some possible “treatments” are medications and physical or speech therapy.

In the United States, about 1 in every 30,000 people has Huntington’s disease.

Klinefelter Syndrome

Klinefelter syndrome is hard to diagnose until the men hit puberty. During this time, the men with XXY chromosomes are “often tall and usually don’t develop secondary sex characteristics, such as facial hair or underarm and pubic hair. The extra X chromosome primarily affects the testes, which produce sperm and the male hormone testosterone” (“Klinefelter” 1). This means that the men are sterile and cannot reproduce.
Klinefelter syndrome is a disorder that only affects males. The disease is caused when a male have an extra X chromosome so instead of having (XY), the males have (XXY). This is typically caused by “nondisjunction. When that egg unites with a normal sperm to form an embryo, that embryo may end up with three copies of the sex chromosomes instead of the normal two. The extra chromosome is then copied into every cell of the body” (“Klinefelter” 1).
The best way to treat this disorder is hormone replacement therapy. Typically “teenagers are given testosterone injections to replace the hormone that would normally be produced by the testes” (“Klinefelter” 1).
Klinefelter syndrome affects between 1 in 500 and 1 in 1,000 people.

Sunday, April 15, 2012

Bibliography

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Board, A.D.A.M. Editorial. "Duchenne Muscular Dystrophy." Duchenne Muscular Dystrophy. U.S. National Library of Medicine, 18 Nov. 0000. Web. 25 Apr. 2012. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001724/>.

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"Progeria." National Human Genome Research Institute (NHGRI). National Institutes of Health. Web. 26 Apr. 2012. <http://www.genome.gov/11007255>.

Staff, Mayo Clinic. "Angelman Syndrome." Mayo Clinic. Mayo Foundation for Medical Education and Research, 17 Jan. 2012. Web. 25 Apr. 2012. <http://www.mayoclinic.com/health/angelman-syndrome/DS01048>.

"Turner Syndrome." Turner Syndrome. The University of Utah. Web. 20 Apr. 2012. <http://learn.genetics.utah.edu/content/disorders/whataregd/turner/index.html>.

"What Is Canavan Disease?" Canavan Foundation. Canavan Fountation. Web. 25 Apr. 2012. <http://www.canavanfoundation.org/canavan.php>.