Sandhoff Disease

Sandhoff Disease

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Sandhoff Disease is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • GM2-gangliosidosis, type ll
  • Hexosaminidases A and B deficiency

Disorder Subdivisions

  • None

General Discussion

Sandhoff disease is a lipid storage disorder characterized by a progressive deterioration of the central nervous system. The clinical symptoms of Sandhoff disease are identical to Tay-Sachs disease. Sandhoff disease is an autosomal recessive genetic disorder caused by an abnormal gene for the beta subunit of the hexosaminidase B enzyme. This gene abnormality results in a deficiency of hexosaminidase A and B that results in accumulation of fats (lipids) called GM2 gangliosides in the neurons and other tissues.

Symptoms

The first symptoms of the infantile form of Sandhoff disease typically begin between the ages of 3 to 6 months. These may include feeding problems, general weakness (lethargy), and an exaggerated startle reflex in response to sudden loud noises. A physician's examination with a special instrument typically reveals round, red spots (cherry macules) in the eyes. Motor delays and mental deterioration are progressive and are characterized by motor weakness, spasticity, heart murmurs, seizures (myoclonic and generalized), blindness, and/or abnormally enlarged spleen (splenomegaly). Firm stroking of the sole of the foot produces a typical reflex response (Babinski sign), and the outer toes spread after the side of the sole of the foot has been stroked.



Juvenile and adult forms of Sandhoff disease have been described that are more variable in the age of onset and severity of symptoms.

Causes

Sandhoff disease is an autosomal recessive genetic disorder caused by an abnormal gene for the beta subunit of the hexosaminidase B (HEXB) enzyme. This gene abnormality results in a deficiency of enzymes called hexosaminidase A and B that are responsible for breaking down GM2 gangliosides made by the nerve cells. The accumulation of GM2 gangliosides in the lysosomes of nerve cells damages the nerve cells and leads to a progressive loss of neurological function.



Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.



All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Sandhoff disease is a very rare disorder that affects males and females in equal numbers. This disorder occurs in people of many different ethnic backgrounds. Sandhoff disease may be more common in the Creole population of northern Argentina, the Metis Indians in Saskatchewan, Canada and individuals of Lebanese ancestry.

Standard Therapies

Diagnosis

Sandhoff disease can be diagnosed by performing an enzyme assay to determine activity of the hexosaminidase A and B enzymes. Affected individuals have absent or reduced activity of both enzymes. Molecular genetic (DNA) testing is available to determine the specific gene mutation that is present in the beta subunit of the Hexosaminidase B gene and confirm the diagnosis.



Treatment

Treatment of Sandhoff disease is symptomatic and supportive and includes nutritional and respiratory therapy. Anticonvulsants may be prescribed to temporarily control seizures. Death from respiratory infection usually occurs by age three for the infantile form of the disease.



Genetic counseling is recommended for affected individuals and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Scriver CR, et a,l eds. The Metabolic Basis of Inherited Disease, 6th Ed. McGraw Hill, 1989:1826-33.



JOURNAL ARTICLES

Frey, LC, Ringel SP and Filley CM. The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis. Arch Neurol 2005;62:989-994.



MacLeod PM, Wood S, Jan JE, et al. Progressive cerebral ataxia, spasticity, psychomotor retardation, and hexosaminidase deficiency in a 10 year-old child: juvenile Sandhoff disease. Neurology 1977;27:571-573.



Rubin M, Karpati G, Wolfe LS, et al. Adult onset motor neuropathy in the juvenile type of hexosaminidase A and B deficiency. J Neurol 1988:87:103-119.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 268800: Last Update:9/1/05.

Resources

National Tay-Sachs and Allied Diseases Association, Inc.

2001 Beacon Street

204

Brookline, MA 02146-4227

USA

Tel: (617)277-4463

Fax: (617)277-0134

Tel: (800)906-8723

Email: info@ntsad.org

Internet: http://www.NTSAD.org



Lighthouse International

111 E 59th St

New York, NY 10022-1202

Tel: (800)829-0500

Email: info@lighthouse.org

Internet: http://www.lighthouse.org



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Sandhoff Disease Informational Website

8825 Hastings Blvd.

Hastings, FL 32145

Tel: (386)202-0018

Email: admin@sandhoff.org

Internet: http://www.sandhoffdisease.webs.com



Hide & Seek Foundation for Lysosomal Disease Research

6475 East Pacific Coast Highway Suite 466

Long Beach, CA 90803

Tel: (877)621-1122

Fax: (866)215-8850

Email: info@hideandseek.org

Internet: http://www.hideandseek.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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