FACTOID # 21: 15% of Army recruits from South Dakota are Native American, which is roughly the same percentage for female Army recruits in the state.
 
 Home   Encyclopedia   Statistics   States A-Z   Flags   Maps   FAQ   About 
   
 
WHAT'S NEW
 

SEARCH ALL

FACTS & STATISTICS    Advanced view

Search encyclopedia, statistics and forums:

 

 

(* = Graphable)

 

 


Encyclopedia > GM2 gangliosidosis
Tay-Sachs disease
ICD-10 code: E75.0
ICD-9 code: 330.1

Tay-Sachs disease (abbreviated TSD, also known as "GM2 gangliosidosis") is a fatal genetic disorder, inherited in an autosomal recessive pattern, in which harmful quantities of a fatty substance called ganglioside GM2 accumulate in the nerve cells in the brain. The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... A genetic disorder, or genetic disease is a disease caused by abnormal expression of one or more genes in a person causing a clinical phenotype. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... Ganglioside is a compound composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (AKA n-acetylneuraminic acid) linked on the sugar chain. ... Neurons (also called nerve cells) are the primary cells of the nervous system. ... Comparative brain sizes In the anatomy of animals, the brain, or encephalon (Greek for in the head), is the higher, supervisory center of the nervous system. ...


The disease is named after the British ophthalmologist Warren Tay who first described the red spot on the retina of the eye in 1881, and the American neurologist Bernard Sachs who described the cellular changes of Tay-Sachs and noted an increased prevalence in the Eastern European Jewish population of 1887. A disease is any abnormal condition of the body or mind that causes discomfort, dysfunction, or distress to the person affected or those in contact with the person. ... Ophthalmology is the branch of medicine which deals with the diseases of the eye and their treatment. ... Human eye cross-sectional view. ... This article needs to be cleaned up to conform to a higher standard of quality. ... 1881 was a common year starting on Saturday (see link for calendar). ... Neurology is the branch of medicine that deals with the nervous system and disorders affecting it. ... Cells in culture, stained for keratin (red) and DNA (green) The cell is the structural and functional unit of all living organisms, and are sometimes called the building blocks of life. ... Pre-1989 division between the West (grey) and Eastern Bloc (orange) superimposed on current national boundaries: Russia (dark orange), other countries of the former USSR (medium orange) and other former communist regimes (light orange). ... The word Jew (Hebrew: יהודי transliterated: Yehudi) is used in many ways, but generally refers to a follower of Judaism, a child of a Jewish mother, or someone of Jewish descent with a connection to Jewish culture or ethnicity; and often a combination of these attributes. ... 1887 is a common year starting on Saturday (click on link for calendar). ...

Contents


Signs and symptoms

Infants with Tay-Sachs disease appear to develop normally for the first six months of life. Then, as nerve cells become distended with fatty material, a relentless deterioration of mental and physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in. Neurons (also called nerve cells) are the primary cells of the nervous system. ... See also Blindness (novel) Blindness can be defined physiologically as the condition of lacking visual perception. ... This article is about hearing impairment in the patholocial sense. ... Swallowing, known scientifically as deglutition, is the reflex in the human body that makes something pass from the mouth, through the esophagus. ... Atrophy is the partial or complete wasting away of a part of the body. ... Paralysis is the complete loss of muscle function for one or more muscle groups. ...


A much rarer form of the disorder which occurs in patients in their twenties and early thirties is characterized by unsteadiness of gait and progressive neurological deterioration. Patients with Tay-Sachs have a "cherry-red" spot in the back of their eyes (the retina). Ataxia (from Greek ataxiā, meaning failure to put in order) is unsteady and clumsy motion of the limbs or trunk due to a failure of the fine coordination of muscle movements. ... Human eye cross-sectional view. ...


Pathogenesis

The condition is caused by insufficient activity of an enzyme called hexosaminidase A that catalyzes the biodegradation of acidic fatty materials known as gangliosides. Gangliosides are made and biodegraded rapidly in early life as the brain develops. Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures hexosaminidase A activity. Both parents must be carriers in order to have an affected child. Prenatal monitoring of pregnancies is available if desired. Ganglioside is a compound composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (AKA n-acetylneuraminic acid) linked on the sugar chain. ... Blood tests are laboratory tests done on blood to gain an appreciation of disease states and the function of organs. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ...


To expand on the genetic basis, Tay-Sachs is an autosomal recessive genetic condition: if both parents are carriers, there is a 25% risk with each pregnancy for an affected child. An autosome is a non-sex chromosome. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ...

Tay-Sachs disease is inherited in the autosomal recessive pattern, depicted above.
Tay-Sachs disease is inherited in the autosomal recessive pattern, depicted above.

The disease results from mutations on chromosome 15 in the HEXA gene encoding the alpha-subunit of the lysosomal enzyme beta-N-acetylhexosaminidase A. This enzyme is necessary for breaking down N-galactosamine from GM2 gangliosides in brain and nerve cells. More than ninety mutations have been identified in the HEXA gene. These consist of base pair insertions, base pair deletions, splice site mutations, and point mutations. All of these mutations alter the protein product. For example, a four base pair insertion in exon 11 results in an altered reading frame for the HEXA gene while a three base pair deletion eliminates the amino acid phenylalanine from the protein product at position 304. A G to C point mutation at amino acid 180 changes the codon UAC to UAG causing termination of the polypeptide. A G to A point mutation at amino acid 170 changes the codon CGA to CAA and CGG to CAG which produces glutamine instead of arginine. A G to C mutation in the splice site of intron 12 has also been identified. This mutation creates a recognition site for the restriction enzyme Ddel resulting in abnormal splicing and the production of aberrant mRNA species. Depiction of autorecessive inheritance in Tay-Sachs disease. ... Depiction of autorecessive inheritance in Tay-Sachs disease. ... In biology, mutations are permanent, sometimes transmissible (if the change is to a germ cell) changes to the genetic material (usually DNA or RNA) of a cell. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Lysosomes are organelles in animal cells that contain digestive enzymes (acid hydrolases) to digest macromolecules. ... Ribbon diagram of the catalytically perfect enzyme TIM. Factor D enzyme crystal prevents the immune system from inappropriately running out of control. ... In molecular biology, two nucleotides on opposite complementary DNA or RNA strands that are connected via hydrogen bonds are called a base pair (often abbreviated bp). ... In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ... The alpha-amino acid Phenylalanine exists in two forms, the D- and L- forms, which are enantiomers (mirror-image molecules) of each other. ... RNA codons. ... Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ... Glutamine (molecular weight: 146. ... Arginine is one of the 20 most common natural amino acids. ... Diagram of the location of introns and exons within a gene. ... The interaction of mRNA in a eukaryote cell. ...


Testing

In populations with a high carrier frequency for TSD, genetic counseling is recommended so genetic testing can be done to detect carriership. Preimplantation genetic diagnosis can be considered in couples where both are carriers. In countries where selective abortion is legal, this method can be contemplated. Genetic counseling generally refers to prenatal counseling done when a genetic condition is suspected in a pregnancy. ... Genetic testing allows the genetic diagnosis of vulnerabilities to inherited diseases, and can also be used to determine a persons ancestry. ... In medicine and (clinical) genetics preimplantation genetic diagnosis (PGD) is a method to test embryos for genetic disorders before they are reimplanted in the uterus. ...


In Orthodox Jewish circles, the organisation Dor Yeshorim carries out an anonymous screening program, preventing the stigma of carriership while decreasing the rate of homozygosity in this population. Orthodox Judaism is the stream of Judaism which adheres to a relatively strict interpretation and application of the laws and ethics first canonized in the Talmud (The Oral Law) and later codified in the Shulkhan Arukh (Code of Jewish Law). It is governed by these works and the Rabbinical commentary... Dor Yeshorim (Hebrew: generation [that is] straight/reliable) is an organization that operates in Orthodox Jewish communities. ... Homozygote cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ...


Proactive testing has been quite effective in eliminating Tays-Sachs occurrence amongst Ashkenazi Jews. Of the 10 babies born with Tay-Sachs in North America in 2003, none were Jews. In Israel, only one child was born with Tay-Sachs in 2003, and preliminary results from early 2005 indicated that none were born with it in 2004.[1] World map showing North America A satellite composite image of North America North America is a continent in the northern hemisphere bordered on the north by the Arctic Ocean, on the east by the North Atlantic Ocean, on the south by the Caribbean Sea, and on the west by the... 2003 (MMIII) is a common year starting on Wednesday of the Gregorian calendar. ... 2005 (MMV) is a common year starting on Saturday of the Gregorian calendar. ... 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ...


Therapy

There is currently no way to effectively cure or treat TSD. Even with the best care TSD children will die by the age of five. However, research is ongoing and several methods of treatment are being investigated, although significant hurdles remain before any of them will be functional. The first treatment method that was investigated by scientists was enzyme replacement therapy, whereby functional Hex A would be injected into the patient to replace the missing enzyme, a process similar to insulin injections. However, the enzyme was found to be too large to be able to pass from the blood into the brain through the blood-brain barrier, where the blood vessels in the brain develop junctions so small that many toxic (or large) molecules cannot enter into nerve cells and cause damage. Researchers also tried instilling Hex A into the cerebrospinal fluid, which bathes the brain. However, neurons are not able to take up the large enzyme efficiently even when it is placed next to the cell, so the treatment is still ineffective. The structure of insulin Red: carbon; green: oxygen; blue: nitrogen; pink: sulfur. ... The blood-brain barrier is a physical barrier between the blood vessels in the central nervous system, and most parts of the central nervous system itself. ... Cerebrospinal fluid (CSF) is a clear bodily fluid that occupies the subarachnoid space in the brain (the space between the skull and the cerebral cortex—more specifically, between the arachnoid and pia layers of the meninges). ...


The most recent option explored by scientists has been gene therapy. However, scientists still believe that they are years away from the technology to transport the genes into neurons, which they say would be just as hard as transporting the enzyme. Currently, most research involving gene therapy involves developing a method of using a viral vector to transfer new DNA into neurons. If the defective genes were to be replaced throughout the brain Tay Sachs could theoretically be cured. Gene therapy using an Adenovirus vector. ... Neurons (also called nerve cells) are the primary cells of the nervous system. ... Space-filling model of a section of DNA molecule Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). ...


Other highly experimental methods being researched involve the manipulation of the brain's metabolism of GM2 gangliosides. One experiment has shown that, using the enzyme sialidase, the genetic defect can be effectively bypassed and GM2 gangliosides metabolized to be almost inconsequential. If a safe pharmacological treatment causing the increased expression of lysosomal sialidase in neurons can be developed, a new form of therapy, essentially curing the disease, could be on the horizon. Ganglioside is a compound composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (AKA n-acetylneuraminic acid) linked on the sugar chain. ... Ganglioside is a compound composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (AKA n-acetylneuraminic acid) linked on the sugar chain. ...


Epidemiology

Historically, Eastern European people of Jewish descent have a high incidence of Tay-Sachs and other lipid storage diseases. In the United States, 1 in 27 Ashkenazi Jews is a recessive carrier, compared to 1 in 200 in the general population [2]. French Canadians and the Cajun community of Louisiana have the same carrier rate as Ashkenazi Jews, one in 27, and among Irish Americans the carrier rate is about one in 50. [3] French Canadian is a term that has several different connotations. ... The Cajuns are an ethnic group consisting essentially of the descendants of Acadians who came from Nova Scotia to Louisiana as a result of their refusal to swear allegiance to the British Crown. ... State nickname: Pelican State Other U.S. States Capital Baton Rouge Largest city New Orleans Governor Kathleen Blanco (D) Senators Mary Landrieu (D) David Vitter (R) Official language(s) None; English and French de facto Area 134,382 km² (31st)  - Land 112,927 km²  - Water 21,455 km² (16%) Population... Irish Americans are residents or citizens of the United States who claim Irish ancestry. ...


In 1991, Jared Diamond theorized that Jews who are heterozygous for Tay-Sachs are resistant to tuberculosis, which was common in the Eastern European ghettos where they lived. Puzzlingly, it has been estimated that it would take more than 300 generations to reach the observed frequency of TSD heterozygosity, yet Ashkenazi Jews have only been a separate group for 70 generations (Shaw and Smith, 1969). Also, one would expect a higher frequency of TSD in other ethnic groups living in the same conditions, which is not the case. 1991 (MCMXCI) is a common year starting on Tuesday of the Gregorian calendar. ... Jared Mason Diamond (born September 10, 1937) is an American author, evolutionary biologist, physiologist, and biogeographer. ... Heterozygote cells are diploid or polyploid and have different alleles at a locus (position) on homologous chromosomes. ... Tuberculous lungs show up on an X-ray image Tuberculosis is an infection with the bacterium Mycobacterium tuberculosis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system (meningitis), lymphatic system, circulatory system (miliary TB), genitourinary system, bones and joints. ... Pre-1989 division between the West (grey) and Eastern Bloc (orange) superimposed on current national boundaries: Russia (dark orange), other countries of the former USSR (medium orange) and other former communist regimes (light orange). ... A ghetto is an area where people from a specific ethnic background or united in a given culture or religion live as a group, voluntarily or involuntarily, in milder or stricter seclusion. ...


References

  • Based in part on the 'Tay-Sachs Disease Information Page' of the National Institute of Neurological Disorders and Stroke (see http://www.ninds.nih.gov/disorders/taysachs/taysachs.htm ).

External links

  • OMIM 272800 and OMIM 606869
  • Tay-Sachs.org
  • National Society of Genetic Counselors
  • YGYH.org

  Results from FactBites:
 
MRE (1914 words)
Gangliosidosis is a lysosomal storage disease which affects primarily the nervous system.
Because GM2 gangliosidosis primarily effects lysosomal storage of neurons, neuronal systems are one of the primary areas affected by the disease.
GM2 gangliosidosis results in the same type of storage defect but is more widely dispersed throughout the brainstem nuclei and cerebellum (Suzuki, 1992).
  More results at FactBites »

 
 

COMMENTARY     


Share your thoughts, questions and commentary here
Your name
Your comments

Want to know more?
Search encyclopedia, statistics and forums:

 


Press Releases |  Feeds | Contact
The Wikipedia article included on this page is licensed under the GFDL.
Images may be subject to relevant owners' copyright.
All other elements are (c) copyright NationMaster.com 2003-5. All Rights Reserved.
Usage implies agreement with terms, 1022, m