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Tay-Sachs disease, variant AB

MedGen UID:
78657
Concept ID:
C0268275
Disease or Syndrome
Synonyms: AB variant; Activator Deficiency/GM2 Gangliosidosis; Activator-deficient Tay-Sachs disease; GM2 Activator Deficiency; GM2 Activator Deficiency Disease; GM2 gangliosidosis, type AB; Gm2-gangliosidosis, ab variant; Hexosaminidase activator deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Tay-Sachs disease, variant AB (71253000); Hexosaminidase activator deficiency (71253000); GM>2< gangliosidosis, type AB (71253000); GM2 activator deficiency (71253000); AB variant (71253000)
 
Gene: GM2A
Cytogenetic location: 5q33.1
OMIM: 272750

Definition

The GM2-gangliosidoses are a group of disorders caused by excessive accumulation of ganglioside GM2 and related glycolipids in the lysosomes, mainly of neuronal cells. GM2-gangliosidosis AB variant is characterized by normal hexosaminidase A (HEXA; 606869) and hexosaminidase B (HEXB; 606873) but the inability to form a functional GM2 activator complex. The clinical and biochemical phenotype of the AB variant is very similar to that of classic Tay-Sachs disease (see 272800) (Gravel et al., 2001). [from OMIM]

Additional description

From GHR
GM2-gangliosidosis, AB variant is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Signs and symptoms of the AB variant become apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with the AB variant experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Children with the AB variant usually live only into early childhood.  http://ghr.nlm.nih.gov/condition/gm2-gangliosidosis-ab-variant

Clinical features

Blindness
MedGen UID:
504525
Concept ID:
CN000580
Finding
Blindness is the condition of lacking visual perception due to physiological or neurological factors.
Paralysis
MedGen UID:
105510
Concept ID:
C0522224
Finding
Paralysis is the loss of muscle function in part of your body. It happens when something goes wrong with the way messages pass between your brain and muscles. Paralysis can be complete or partial. It can occur on one or both sides of your body. It can also occur in just one area, or it can be widespread. Paralysis of the lower half of your body, including both legs, is called paraplegia. Paralysis of the arms and legs is quadriplegia. . Most paralysis is due to strokes or injuries such as spinal cord injury or a broken neck. Other causes of paralysis include: -Nerve diseases such as amyotrophic lateral sclerosis. - Autoimmune diseases such as Guillain-Barre syndrome. - Bell's palsy, which affects muscles in the face. Polio used to be a cause of paralysis, but polio no longer occurs in the U.S.
Dementia
MedGen UID:
504574
Concept ID:
CN000683
Finding
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Exaggerated startle response
MedGen UID:
505176
Concept ID:
CN002058
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Aspiration
MedGen UID:
409585
Concept ID:
C1963221
Finding
The untoward medical consequence (or experience) of an unintentional inhalation of oro-pharyngeal or gastric contents into trachea or the lung airways.
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGTay-Sachs disease, variant AB

Recent clinical studies

Etiology

Lemieux MJ, Mark BL, Cherney MM, Withers SG, Mahuran DJ, James MN
J Mol Biol 2006 Jun 16;359(4):913-29. Epub 2006 Apr 27 doi: 10.1016/j.jmb.2006.04.004. [Epub ahead of print] PMID: 16698036Free PMC Article
Cordeiro P, Hechtman P, Kaplan F
Genet Med 2000 Nov-Dec;2(6):319-27. doi: 10.109700125817-200011000-00003. PMID: 11339652
Wright CS, Li SC, Rastinejad F
J Mol Biol 2000 Dec 1;304(3):411-22. doi: 10.1006/jmbi.2000.4225. PMID: 11090283
Asfaw B, Schindler D, Ledvinová J, Cerný B, Smíd F, Conzelmann E
J Lipid Res 1998 Sep;39(9):1768-80. PMID: 9741689
Sandhoff K, Christomanou H
Hum Genet 1979;50(2):107-43. PMID: 116955

Diagnosis

Sobek AK, Evers C, Dekomien G
Mol Cell Probes 2013 Feb;27(1):32-7. Epub 2012 Aug 27 doi: 10.1016/j.mcp.2012.08.007. [Epub ahead of print] PMID: 23010210
Conzelmann E, Nehrkorn H, Kytzia HJ, Sandhoff K, Macek M, Lehovský M, Elleder M, Jirásek A, Kobilková J
Pediatr Res 1985 Nov;19(11):1220-4. PMID: 2933632
Pullarkat RK, Reha H, Beratis NG
Pediatrics 1981 Jul;68(1):106-8. PMID: 7243492
Goldman JE, Yamanaka T, Rapin I, Adachi M, Suzuki K, Suzuki K
Acta Neuropathol 1980;52(3):189-202. PMID: 6255724
de Baecque CM, Suzuki K, Rapin I, Johnson AB, Whethers DL
Acta Neuropathol 1975 Dec 19;33(3):207-26. PMID: 174379

Therapy

Tsuji D, Higashine Y, Matsuoka K, Sakuraba H, Itoh K
Clin Chim Acta 2007 Mar;378(1-2):38-41. Epub 2006 Oct 24 doi: 10.1016/j.cca.2006.10.010. [Epub ahead of print] PMID: 17196574

Prognosis

Sinici I, Yonekawa S, Tkachyova I, Gray SJ, Samulski RJ, Wakarchuk W, Mark BL, Mahuran DJ
PLoS One 2013;8(3):e57908. Epub 2013 Mar 4 doi: 10.1371/journal.pone.0057908. PMID: 23483939Free PMC Article
Hechtman P, Gordon BA, Ng Ying Kin NM
Pediatr Res 1982 Mar;16(3):217-22. PMID: 6801612
Goldman JE, Yamanaka T, Rapin I, Adachi M, Suzuki K, Suzuki K
Acta Neuropathol 1980;52(3):189-202. PMID: 6255724
Purpura DP, Suzuki K
Brain Res 1976 Oct 29;116(1):1-21. PMID: 824017

Clinical prediction guides

Sinici I, Yonekawa S, Tkachyova I, Gray SJ, Samulski RJ, Wakarchuk W, Mark BL, Mahuran DJ
PLoS One 2013;8(3):e57908. Epub 2013 Mar 4 doi: 10.1371/journal.pone.0057908. PMID: 23483939Free PMC Article
Sobek AK, Evers C, Dekomien G
Mol Cell Probes 2013 Feb;27(1):32-7. Epub 2012 Aug 27 doi: 10.1016/j.mcp.2012.08.007. [Epub ahead of print] PMID: 23010210
Bierfreund U, Lemm T, Hoffmann A, Uhlhorn-Dierks G, Childs RA, Yuen CT, Feizi T, Sandhoff K
Neurochem Res 1999 Feb;24(2):295-300. PMID: 9972878
Pullarkat RK, Reha H, Beratis NG
Pediatrics 1981 Jul;68(1):106-8. PMID: 7243492
de Baecque CM, Suzuki K, Rapin I, Johnson AB, Whethers DL
Acta Neuropathol 1975 Dec 19;33(3):207-26. PMID: 174379

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