Hurler+Syndrome+-+Mr.+Currence

=Hurler Syndrome=

Introduction
Hurler syndrome has several other names including: -Alpha-L-iduronate deficiency -Mucopolysaccharidosis type I -MPS - I H -Gargoylism

Hurler syndrome is a rare, inherited, metabolic disorder. Hurler syndrome exists when an individual is missing the enzyme responsible for breaking down long chains of sugar molecules called glycosaminoglycans (GAGs). When these chains can not be metabolized naturally within the body, they can build up to toxic levels resulting in damage to organs.

Cause
The human body naturally makes the protein/enzyme alpha-L-iduronate (IDUA) which is responible for breaking down long sugar chains called GAGs. GAGs are made and used by the body when building and repairing tissues and bones, so they are naturally formed and broken down everyday. When a mutation in the gene that codes for IDUA enzyme prevents it from being produced in sufficient quantity, the GAGs can build up within organs, including the heart, and cause permanant damage.

Hurler syndrome is caused by a mutation in the gene codes for IDUA production. It is an autosomal ( not sex-linked) recessive diesease, so a person suffering from Hurler syndrome must have recieved a copy of the mutated gene from both his mother and father. If a person is heterozygous for Hurler syndrome they are considered a carrier, but do not express the disease. Carriers can pass the mutated gene on to their children. The gene for IDUA production is found on the 4th chromosome at the gene map locus 4p16.3. and the disease is usually caused by multiple missense and frameshift mutations which insert stop codons into the 19,000 base pair !DUA gene.

Signs and Symptoms
Hurler syndrome is actually one of three levels of MPS-I. Hurler is the most severe of the three levels, with Scheie syndrome being the least severe, and Hurler-Scheie syndrome being the phenotypic intermediate of the two. Hurler syndrome is both chronic and progressive, which means that once symptoms appear, they continue to get worse as the patient ages. Infants usually appear normal at birth, but signs and symptoms develop over time as the GAGs build up within the body and damage organs and tissues. The symptoms generally appear during the first year of life, and result in death between the age of 5 and 10 if the disease is not treated. Signs include: -Coursening facial features (nose, lips, and ears) -Developmental delay and/or mental retardation -Heart problems -Hearing problems and/or ear infections -Skull deformation including large head, wide forehead, and/or heavy brow -Bone deformation including hips, rips, long bones of the legs, fingers, and/or spine which lead to short stature -Respiratory problems
 * [[image:hurler3.gif caption="X-ray of child's hand who suffers from Hurler syndrome"]]

The hand of a Hurler child (above). Note "bullet" shaped finger bones and incomplete development. At right, a normal child's hand. || || on 2/15/2009 || Downloaded from http://www.madsci.org/cgi-bin/cgiwrap/~lynn/image?return=&name=hand_wrist&show_all=1&search= on 2/15/2009 || on 2/15/2009 ||
 * Downloaded from: [|www.stevensorenson.com/ residents6/hurler3.gif]
 * [[image:Cooper1.jpg caption="Danielle Cooper suffered from Hurler Syndrome. she survived until the age of 5."]] ||
 * Downloaded from: http://www.mpssociety.org.au/mps_picture_gallery.htm

Tests
An infants urine can be tested for certain molecules that would normally be absent if IDUA was present and functioning properly. These molecules can be cetain sulfates that are present in Hurler sufferers, or the GAG molecules themselves. There are also blood test available that check for the presence of IDUA. X-rays can be examined to look for poor bone development, and EKG (Electrocardiogram) can be used to check for irregular heartbeat. Because Hurler syndrome is genetic, it can also be identified while the fetus is still in the womb. A swab from the fetus can be checked for IDUA activity, and if a sibling already suffers from Hurler syndrome, then a DNA comparison can be conducted to look for identical gene mutations.

Treatment
There is no cure for Hurler syndrome. Treatment follows two paths, but the goal is always to replace the IDUA enzyme in the patient early enough to prevent GAG build up. Currently research is being done with gene therapy, although this is not currently an approved treatment. In many cases, BMT and enzyme replacement therapy are used together to minimize the impact of Hurler syndrome and can prevent any symptoms from developing.

Bone marrow transplant (BMT) or cord blood transplant
- The goal with this treatment is to remove the cells responsible for producing IDUA carrying the mutated gene and replace them with healthy cells. In some patients bone marrow transplant coupled with full-body chemotherapy in addtion to radiation has shown positive results in slowing progression and extending lifespan. Patients may still suffer from the chronic and progressive nature of Hurler syndrome, but at a much slower rate. Some patients suffer no mental retardation and near normal bone growth, but only if the transplant is performed at an early enough stage of the disease.

Enzyme Replacement Therapy
- Patients have been treated with weekly injections of artificial IDUA enzyme. Other treatments, including the drug Laronidase, are administered by IV. Enzyme replacement therapy has been shown to reduce the physiological effects of Hurler Syndrome, but shown no significant effect on neurological symptoms, including mental retardation. For this reason enzyme replacement therapy is often used in patients who show no sign of delayed mental development.

Gene Therapy
- In simple bacteria, a retroviral DNA strand has been created that effectively codes for IDUA production. In bacteria with the Hurler mutation, IDUA production has been detected after the bacteria are treated with the retroviral DNA strand. Research and development continues using human fibroblast stem cells, and results are promising. on 2/15/2009 ||
 * [[image:hurler_ped_large.gif caption="Graph of Hurler Survival after BMT"]] ||
 * Downloaded from: http://www.marrow.org/PATIENT/Undrstnd_Disease_Treat/Lrn_about_Disease/Metabolic_Storage/Hurler_and_Tx/index.html

Prevention/Prognosis
There is no prevention for Hurler syndrome except for carriers to undergo genetic testing and couples therapy before deciding to have children. The Prognosis for Hurler syndrome is poor. Left untreated most patients have a life expectancy of 5 to 10 years. Current efforts in the area of enzyme replacement therapy are promising, and the future may show improvements in methods and results of this and other treatments.

Interesting Facts/Statistics/Demographics
Hurler Syndrome is named after Gertrude Hurler, who first identified the disease is a boy and a girl in 1919. The current rates of Hurler inheritance is approximately 1 to 2 per 100,000 births. Many studies of Hurler Syndrom have been conducted on a vairety of racial backgrounds, and although every race studied is found to be succeptable to the disease, novel mutations are found within individual subgroups within the studies.

Work Cited
Australian MPS Society. (n.d.). Retrieved February 16, 2009, from http://www.mpssociety.org.au/

Hurler’s syndrome. (2009). In //Encyclopædia Britannica//. Retrieved February 15, 2009, from Encyclopædia Britannica Online: http://www.britannica.com/EBchecked/topic/277277/Hurler-syndrome

Hurler syndrome. (2004, August 8). //Madisons Foundation - Moms And Dads In Search Of Needed Support// Retrieved February 15, 2009, from http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,451/

Hurler syndrome. (2007, May 22). In //MedlinePlus Medical Encyclopedia//. Retrieved February 15, 2009, from http://www.nlm.nih.gov/medlineplus/ency/article/001204.htm

Hurler Syndrome. (2007, October 1). In //Online Mendelian Inheritance in Man: Johns Hopkins University//. Retrieved February 15, 2009, from http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607014

Hurler's Syndrome and Transplant -- patient information. (February 2006). //National Marrow Donor Program//. Retrieved February 15, 2009, from http://www.marrow.org/PATIENT/Undrstnd_Disease_Treat/Lrn_about_Disease/Metabolic_Storage/Hurler_and_Tx/index.html

Hurler syndrome - Overview. (2008). //University of Maryland Medical Center//. Retrieved February 15, 2009, from http://www.umm.edu/ency/article/001204.htm

National MPS Society | Home. (n.d.). Retrieved February 15, 2009, from http://www.mpssociety.org/