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Sandhoff disease

MedGen UID:
11313
Concept ID:
C0036161
Disease or Syndrome
Synonyms: Beta-hexosaminidase-beta-subunit deficiency; GM2 gangliosidosis, type 2; GM2-GANGLIOSIDOSIS, TYPE II; Hexosaminidase A and B deficiency Disease; HEXOSAMINIDASES A AND B DEFICIENCY; Sandhoff-Jatzkewitz-Pilz disease; Total hexosaminidase deficiency
SNOMED CT: Sandhoff disease (23849003); GM>2< gangliosidosis, type 2 (23849003); Hexosaminidase A AND B deficiency (23849003); Total hexosaminidase deficiency (23849003); O variant (23849003)
 
Gene: HEXB
Cytogenetic location: 5q13.3
OMIM: 268800

Definition

Sandhoff disease is a progressive neurodegenerative disorder characterized by an accumulation of GM2 gangliosides, particularly in neurons, and is clinically indistinguishable from Tay-Sachs disease (272800). [from OMIM]

Additional description

From GHR
Sandhoff disease is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. The most common and severe form of Sandhoff disease becomes 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 Sandhoff disease 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. Some affected children also have enlarged organs (organomegaly) or bone abnormalities. Children with the severe infantile form of Sandhoff disease usually live only into early childhood. Other forms of Sandhoff disease are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease.  http://ghr.nlm.nih.gov/condition/sandhoff-disease

Clinical features

Macroglossia
MedGen UID:
504371
Concept ID:
CN000154
Finding
Increased length and width of the tongue.
Visual impairment
MedGen UID:
504469
Concept ID:
CN000473
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Blindness
MedGen UID:
504525
Concept ID:
CN000580
Finding
Blindness is the condition of lacking visual perception due to physiological or neurological factors.
Abnormality of the macula
MedGen UID:
446392
Concept ID:
CN001036
Finding
An abnormality of the `macula lutea` (FMA:58637) is an oval-shaped highly pigmented yellow spot near the center of the retina.
Hearing impairment
MedGen UID:
446352
Concept ID:
CN000341
Finding
A `decreased magnitude` (PATO:0002018) of the `sensory perception of sound` (GO:0007605).
Orthostatic hypotension
MedGen UID:
43803
Concept ID:
C0020651
Finding
A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Fasciculations
MedGen UID:
505219
Concept ID:
CN002161
Finding
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
Abnormality of movement
MedGen UID:
506445
Concept ID:
CN116921
Finding
An abnormality of movement with a neurological basis characterized by changes in coordination and speed of voluntary movements.
Skeletal dysplasia
MedGen UID:
505316
Concept ID:
CN002411
Finding
A general term describing features characterized by abnormal development of bones and connective tissues.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Hepatosplenomegaly
MedGen UID:
504839
Concept ID:
CN001310
Finding
Simultaneous `enlargement` (PATO:0000586) of the `liver` (FMA:7197) and `spleen` (FMA:7196).
Chronic diarrhea
MedGen UID:
505061
Concept ID:
CN001835
Finding
The presence of chronic `diarrhea` (HP:0002014), which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally `increased size` (PATO:0000586) of the `liver` (FMA:7197).
Episodic abdominal pain
MedGen UID:
428302
Concept ID:
CN002336
Finding
An `intermittent` (PATO:0000690) form of `abdominal pain` (HP:0002027).
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Excessive sweating. In the localized type, the most frequent sites are the palms, soles, axillae, inguinal folds, and the perineal area. Its chief cause is thought to be emotional. Generalized hyperhidrosis may be induced by a hot, humid environment, by fever, or by vigorous exercise.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
hypertrophy or enlargement of the heart.
Orthostatic hypotension
MedGen UID:
43803
Concept ID:
C0020651
Finding
A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.
Congestive heart failure
MedGen UID:
504881
Concept ID:
CN001488
Finding
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Abnormality of glycosphingolipid metabolism
MedGen UID:
425254
Concept ID:
CN003844
Finding
An abnormality of `glycosphingolipid` (CHEBI:24402) metabolism.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Hepatosplenomegaly
MedGen UID:
504839
Concept ID:
CN001310
Finding
Simultaneous `enlargement` (PATO:0000586) of the `liver` (FMA:7197) and `spleen` (FMA:7196).
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
A reduction in the strength of one or more muscles.
Macroglossia
MedGen UID:
504371
Concept ID:
CN000154
Finding
Increased length and width of the tongue.

Recent clinical studies

Etiology

Gaignard P, Fagart J, Niemir N, Puech JP, Azouguene E, Dussau J, Caillaud C
Gene 2013 Jan 10;512(2):521-6. Epub 2012 Oct 6 doi: 10.1016/j.gene.2012.09.124. [Epub ahead of print] PMID: 23046579
Gort L, de Olano N, Macías-Vidal J, Coll MA; Spanish GM2 Working Group
Gene 2012 Sep 10;506(1):25-30. Epub 2012 Jul 10 doi: 10.1016/j.gene.2012.06.080. [Epub ahead of print] PMID: 22789865
Zampieri S, Filocamo M, Buratti E, Stroppiano M, Vlahovicek K, Rosso N, Bignulin E, Regis S, Carnevale F, Bembi B, Dardis A
Neurogenetics 2009 Feb;10(1):49-58. Epub 2008 Aug 29 doi: 10.1007/s10048-008-0145-1. [Epub ahead of print] PMID: 18758829
Wang SZ, Cachón-González MB, Stein PE, Lachmann RH, Corry PC, Wraith JE, Cox TM
Mol Genet Metab 2008 Dec;95(4):236-8. Epub 2008 Oct 18 doi: 10.1016/j.ymgme.2008.08.007. [Epub ahead of print] PMID: 18930675
Cantor RM, Roy C, Lim JS, Kaback MM
Am J Hum Genet 1987 Jul;41(1):16-26. PMID: 2955697Free PMC Article

Diagnosis

Kang SY, Song SK, Lee JS, Choi JC, Kang JH
J Clin Neuromuscul Dis 2013 Dec;15(2):47-51. doi: 10.1097/CND.0000000000000014. PMID: 24263030
Fitterer BB, Antonishyn NA, Hall PL, Lehotay DC
Genet Test Mol Biomarkers 2012 May;16(5):401-5. Epub 2011 Dec 22 doi: 10.1089/gtmb.2011.0215. [Epub ahead of print] PMID: 22191674
Seshadri R, Christopher R, Arvinda HR
Neurology 2011 Aug 2;77(5):e34. doi: 10.1212/WNL.0b013e318227b215. PMID: 21810694
Sakpichaisakul K, Taeranawich P, Nitiapinyasakul A, Sirisopikun T
J Med Assoc Thai 2010 Sep;93(9):1088-92. PMID: 20873083
Delnooz CC, Lefeber DJ, Langemeijer SM, Hoffjan S, Dekomien G, Zwarts MJ, Van Engelen BG, Wevers RA, Schelhaas HJ, van de Warrenburg BP
J Neurol Neurosurg Psychiatry 2010 Sep;81(9):968-72. doi: 10.1136/jnnp.2009.177089. PMID: 20798201

Therapy

Zampieri S, Cattarossi S, Oller Ramirez AM, Rosano C, Lourenco CM, Passon N, Moroni I, Uziel G, Pettinari A, Stanzial F, de Kremer RD, Azar NB, Hazan F, Filocamo M, Bembi B, Dardis A
PLoS One 2012;7(7):e41516. Epub 2012 Jul 27 doi: 10.1371/journal.pone.0041516. PMID: 22848519Free PMC Article
Matsuoka K, Tsuji D, Aikawa S, Matsuzawa F, Sakuraba H, Itoh K
Mol Ther 2010 Aug;18(8):1519-26. Epub 2010 Jun 22 doi: 10.1038/mt.2010.113. [Epub ahead of print] PMID: 20571546Free PMC Article
Batista L, Miller F, Clave C, Arfi A, Douillard-Guilloux G, Couraud PO, Caillaud C
Neurobiol Dis 2010 Mar;37(3):656-60. Epub 2009 Dec 18 doi: 10.1016/j.nbd.2009.12.001. [Epub ahead of print] PMID: 20005954
Tallaksen CM, Berg JE
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S289-93. Epub 2009 Nov 4 doi: 10.1007/s10545-009-1224-7. [Epub ahead of print] PMID: 19898953
Wortmann SB, Lefeber DJ, Dekomien G, Willemsen MA, Wevers RA, Morava E
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S307-11. Epub 2009 Nov 4 doi: 10.1007/s10545-009-1261-2. [Epub ahead of print] PMID: 19898952

Prognosis

Abo-Ouf H, Hooper AW, White EJ, van Rensburg HJ, Trigatti BL, Igdoura SA
Hum Mol Genet 2013 Oct 1;22(19):3960-75. Epub 2013 May 31 doi: 10.1093/hmg/ddt250. [Epub ahead of print] PMID: 23727835
Gaignard P, Fagart J, Niemir N, Puech JP, Azouguene E, Dussau J, Caillaud C
Gene 2013 Jan 10;512(2):521-6. Epub 2012 Oct 6 doi: 10.1016/j.gene.2012.09.124. [Epub ahead of print] PMID: 23046579
Sakpichaisakul K, Taeranawich P, Nitiapinyasakul A, Sirisopikun T
J Med Assoc Thai 2010 Sep;93(9):1088-92. PMID: 20873083
Masciullo M, Santoro M, Modoni A, Ricci E, Guitton J, Tonali P, Silvestri G
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S355-61. Epub 2010 Sep 4 doi: 10.1007/s10545-010-9186-3. [Epub ahead of print] PMID: 20821051
Wortmann SB, Lefeber DJ, Dekomien G, Willemsen MA, Wevers RA, Morava E
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S307-11. Epub 2009 Nov 4 doi: 10.1007/s10545-009-1261-2. [Epub ahead of print] PMID: 19898952

Clinical prediction guides

Gaignard P, Fagart J, Niemir N, Puech JP, Azouguene E, Dussau J, Caillaud C
Gene 2013 Jan 10;512(2):521-6. Epub 2012 Oct 6 doi: 10.1016/j.gene.2012.09.124. [Epub ahead of print] PMID: 23046579
Keilani S, Lun Y, Stevens AC, Williams HN, Sjoberg ER, Khanna R, Valenzano KJ, Checler F, Buxbaum JD, Yanagisawa K, Lockhart DJ, Wustman BA, Gandy S
J Neurosci 2012 Apr 11;32(15):5223-36. doi: 10.1523/JNEUROSCI.4860-11.2012. PMID: 22496568
Tancini B, Magini A, Latterini L, Urbanelli L, Ciccarone V, Elisei F, Emiliani C
Mol Cell Biochem 2010 Feb;335(1-2):273-82. Epub 2009 Oct 2 doi: 10.1007/s11010-009-0277-0. [Epub ahead of print] PMID: 19823769
Wortmann SB, Lefeber DJ, Dekomien G, Willemsen MA, Wevers RA, Morava E
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S307-11. Epub 2009 Nov 4 doi: 10.1007/s10545-009-1261-2. [Epub ahead of print] PMID: 19898952
Baek RC, Martin DR, Cox NR, Seyfried TN
Lipids 2009 Mar;44(3):197-205. Epub 2008 Nov 26 doi: 10.1007/s11745-008-3268-0. [Epub ahead of print] PMID: 19034545Free PMC Article

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