Authors' recommendations: Tay-Sachs disease (TSD) is an inherited fatal neurodegenerative disease, the prototype of a group of disorders called hexosaminidase A deficiency or GM2 gangliosidosis. Hexosaminidase A deficiencies are caused by excessive storage of a cell membrane glycolipid, GM2 ganglioside, within the cell lysosomes. Infants with TSD typically appear developmentally normal in the first months of life. Between 3 and 6 months of age, weakness and loss of motor skills become apparent, accompanied by decreased social interaction and visual attentiveness, and increased startle response to sharp noise. Typical clinical findings include the distinctive "cherry-red spot" in one or both eyes, liver and spleen of normal size, low muscle tone, involuntary muscle contractions, and overactive reflexes. As neurodegeneration progresses, motor skills are lost and overall movement decreases, vision deteriorates, and seizures are common by age 12 months. Disease progresses further in the second year with difficulty swallowing and more frequent and severe seizure activity, resulting in a vegetative state. Death from pneumonia generally occurs between ages 2 and 4 years, although improvements in supportive care may prolong survival. Historically, TSD was most common in the Ashkenazi Jewish population, occurring in approximately 1 in 3600 births prior to the implementation of targeted carrier screening programs. Comparatively, occurrence of TSD in the general population is approximately 1 in 360,000 births, although certain ethnic groups such as French Canadians have a higher incidence. With the success of Ashkenazi Jewish carrier screening, the majority of cases of infantile TSD in North America now occur in non–Ashkenazi Jewish individuals. TSD and other hexosaminidase A deficiencies result from genetic abnormalities, or variants, in the HEXA gene, which encodes the alpha subunit of the HEX A enzyme. The level of HEX A enzyme is inversely correlated with disease severity in hexosaminidase A deficiencies. The disease is inherited recessively, such that individuals who inherit two variant copies of the HEXA gene are afflicted with disease, while individuals who inherit one variant copy are unaffected disease carriers. Patients with the most severe form of hexosaminidase A deficiency, infantile TSD, have two nonfunctioning HEXA variants, and therefore, a complete lack of HEX A enzyme activity. HEXA variants associated with severe disease are most common, but some HEXA variants are associated with milder disease forms with later onset and slower disease progression. There are also HEXA variants that are not associated with disease (i.e., polymorphisms). Targeted testing for TSD typically involves testing for a panel of the most common HEXA gene variants. Although such targeted HEXA gene testing is often included in what are called Ashkenazi Jewish screening panels, some of the included variants are generally not found in Ashkenazi Jews but are common in other populations. Approximately 40% to 50% of non-Jewish carriers do not have common variants, however, and targeted testing may not yield conclusive results. Full-gene sequencing is therefore common in cases where ancestry is non-Jewish or unknown. Treatment of TSD is primarily supportive and consists of providing adequate hydration and nutrition, coping with infectious disease, maintaining respiratory and digestive systems, and controlling seizures.

Project Status: Completed

Year Published: 2011

URL for published report: http://www.hayesinc.com/hayes/crd/?crd=13226

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

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Contact Email: saleinfo@hayesinc.com

Copyright: 2011 Winifred S. Hayes, Inc