MCID: SND007
MIFTS: 51

Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Metabolic diseases

Aliases & Classifications for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

MalaCards integrated aliases for Sandhoff Disease, Infantile, Juvenile, and Adult Forms:

Name: Sandhoff Disease, Infantile, Juvenile, and Adult Forms 54 13 38
Sandhoff Disease 38 12 72 50 24 25 51 56 71 29 52 42 14 69
Total Hexosaminidase Deficiency 50 25 69
Beta-Hexosaminidase-Beta-Subunit Deficiency 50 25
Hexosaminidase a and B Deficiency Disease 50 25
Sandhoff-Jatzkewitz-Pilz Disease 50 25
Gm2 Gangliosidosis, Type 2 50 25
B Variant of the Hexosaminidase Gm2 Gangliosidosis 72
Hexosaminidases a and B Deficiency, Infantile Form 56
Hexosaminidases a and B Deficiency, Juvenile Form 56
Hexosaminidases a and B Deficiency, Adult Form 56
Infantile Gm2 Gangliosidosis 0 Variant 56
Juvenile Gm2 Gangliosidosis 0 Variant 56
Hexosaminidases a and B Deficiency 56
Adult Gm2 Gangliosidosis 0 Variant 56
Hexosaminidase a and B Deficiency 71
Sandhoff Disease, Infantile Form 56
Sandhoff Disease, Juvenile Form 56
Gm2 Gangliosidosis 0 Variant 56
Sandhoff Disease, Adult Form 56
Sandhoff Jatzkewitz Disease 12
Gm2 Gangliosidosis, Type Ii 25
Gm2-Gangliosidosis 2 71
Gangliosidoses, Gm2 69
Gm2 Gangliosidosis 24
Gm2g2 71
Sd 71

Characteristics:

Orphanet epidemiological data:

56
sandhoff disease
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Portugal),1-9/1000000 (Netherlands),1-9/1000000 (Czech Republic),1-9/1000000 (Australia),1-9/1000000 (Turkey),1-9/1000000 (United States),1-9/1000000 (Europe),1-9/1000000 (Sweden); Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: adolescent,early childhood,late childhood;

OMIM:

54
Inheritance:
autosomal recessive with multiple alleles and compounds


Classifications:



Summaries for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

NINDS : 51 Sandhoff disease is a rare, inherited lipid storage disorder that progressively destroys nerve cells in the brain and spinal cord.  It is caused by a deficiency of the enzyme beta-hexosaminidase, which results in the harmful accumulation of certain fats (lipids) in the brain and other organs of the body. Sandhoff disease is a severe form of Tay-Sachs disease, the incidence of which had been particularly high in people of Eastern European and Ashkenazi Jewish descent, but Sandhoff disease is not limited to any ethnic group. Onset of the disorder usually occurs at 6 months of age. Neurological symptoms may include progressive nervous system deterioration, problems initiating and controlling muscles and movement, increased startle reaction to sound, early blindness, seizures, spasticity (non-voluntary and awkward movement), and myoclonus (shock-like contractions of a muscle.  Other symptoms may include macrocephaly (an abnormally enlarged head), cherry-red spots in the eyes, frequent respiratory infections, doll-like facial appearance, and an enlarged liver and spleen. Each parent must carry the defective gene and pass it on to the child.  Individuals who carry only one copy of the mutated gene typically do not show signs and symptoms of the disorder.

MalaCards based summary : Sandhoff Disease, Infantile, Juvenile, and Adult Forms, also known as sandhoff disease, is related to gm2 gangliosidosis, 0 variant and hemoglobin sd, and has symptoms including failure to thrive, ataxia and recurrent respiratory infections. An important gene associated with Sandhoff Disease, Infantile, Juvenile, and Adult Forms is HEXB (Hexosaminidase Subunit Beta), and among its related pathways/superpathways are Sphingolipid metabolism and Keratan sulfate/keratin metabolism. Affiliated tissues include brain, spinal cord and eye, and related phenotypes are craniofacial and liver/biliary system

NIH Rare Diseases : 50 sandhoff disease is an inherited lipid storage 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. other forms of sandhoff disease have been described where much milder signs and symptoms begin in childhood, adolescence, or adulthood. these forms are very rare. sandhoff disease is caused by mutations in the hexb gene. these mutations cause a deficiency of the enzymebeta-hexosaminidase, which results in the accumulation of certain fats (lipids) in the brain and other organs of the body. sandhoff disease is inherited in an autosomal recessive manner.  last updated: 10/19/2011

UniProtKB/Swiss-Prot : 71 GM2-gangliosidosis 2: An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. Clinically indistinguishable from GM2-gangliosidosis type 1, presenting startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula.

Genetics Home Reference : 25 Sandhoff disease is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord.

OMIM : 54
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). (268800)

Wikipedia : 72 Sandhoff disease, also known as Sandhoff–Jatzkewitz disease, variant 0 of GM2-Gangliosidosis or... more...

Related Diseases for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Diseases related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 55)
id Related Disease Score Top Affiliating Genes
1 gm2 gangliosidosis, 0 variant 12.2
2 hemoglobin sd 12.0
3 shwachman-diamond syndrome 11.7
4 salla disease 11.4
5 tay-sachs disease 11.2
6 trichohepatoenteric syndrome 1 11.0
7 semantic dementia 11.0
8 rheumatic encephalitis 10.9
9 sydenham chorea 10.9
10 generalized gangliosidoses 10.9
11 macrocephaly/autism syndrome 10.8
12 desbuquois dysplasia 1 10.8
13 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 10.8
14 microcephaly 1, primary, autosomal recessive 10.8
15 gm1-gangliosidosis, type i 10.8
16 multiple system atrophy 10.8
17 microcephaly 17, primary, autosomal recessive 10.6
18 acid-labile subunit, deficiency of 10.6
19 microcephaly 5, primary, autosomal recessive 10.6
20 lissencephaly 4 10.6
21 desbuquois dysplasia 2 10.6
22 macular dystrophy, vitelliform, 5 10.6
23 nanophthalmos 4 10.6
24 frontotemporal lobar degeneration with ubiquitin-positive inclusions 10.6
25 free sialic acid storage disorders 10.6
26 macular dystrophy, vitelliform, 4 10.6
27 microcephaly 10, primary, autosomal recessive 10.6
28 short stature, idiopathic familial 10.6
29 mental retardation and microcephaly with pontine and cerebellar hypoplasia 10.6
30 short stature with nonspecific skeletal abnormalities 10.6
31 neuronitis 10.2
32 malignant glioma 10.1 HEXA HEXB
33 motor neuron disease 10.0
34 splenic manifestation of prolymphocytic leukemia 9.9 HEXA NPC1
35 uterine corpus cancer 9.8 HEXA NPC1
36 retinitis 9.8
37 ataxia 9.8
38 bronchopulmonary dysplasia 9.8
39 phenylketonuria 9.7
40 diarrhea 9.7
41 spasticity 9.7
42 central nervous system disease 9.7
43 endotheliitis 9.7
44 infertility 9.7
45 nervous system disease 9.7
46 neuropathy 9.7
47 cerebellar ataxia 9.7
48 achalasia 9.7
49 autonomic dysfunction 9.7
50 ovarian clear cell malignant adenofibroma 9.6 HEXA NPC1

Graphical network of the top 20 diseases related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms:



Diseases related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Symptoms & Phenotypes for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Symptoms via clinical synopsis from OMIM:

54

Facies:
coarse facies
doll-like face

Neuro:
dysarthria
hyperreflexia
cerebellar ataxia
fasciculations
orthostatic hypotension
more
Cranium:
macrocephaly

GU:
impotence
mild urinary incontinence

Eyes:
early blindness
cherry red spots

Skin:
impaired sweating

Lab:
hexosaminidase b beta chain deficiency

Tongue:
macroglossia

Cardiac:
cardiomegaly

Muscle:
muscle wasting
infantile muscle weakness

GI:
hepatosplenomegaly
chronic diarrhea
episodic abdominal pain

Skel:
high lumbar gibbus

Misc:
lethal usually by age 3 years
intolerance to heat


Clinical features from OMIM:

268800

Human phenotypes related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms:

56 32 (show all 35)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 56 32 hallmark (90%) Very frequent (99-80%) HP:0001508
2 ataxia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001251
3 recurrent respiratory infections 56 32 frequent (33%) Frequent (79-30%) HP:0002205
4 hepatomegaly 56 32 frequent (33%) Frequent (79-30%) HP:0002240
5 splenomegaly 56 32 frequent (33%) Frequent (79-30%) HP:0001744
6 seizures 56 32 hallmark (90%) Very frequent (99-80%) HP:0001250
7 kyphosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0002808
8 muscle weakness 56 32 frequent (33%) Frequent (79-30%) HP:0001324
9 macrocephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000256
10 blindness 56 32 hallmark (90%) Very frequent (99-80%) HP:0000618
11 full cheeks 56 32 frequent (33%) Frequent (79-30%) HP:0000293
12 congestive heart failure 56 32 occasional (7.5%) Occasional (29-5%) HP:0001635
13 skeletal dysplasia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002652
14 progressive psychomotor deterioration 56 32 hallmark (90%) Very frequent (99-80%) HP:0007272
15 hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000365
16 motor deterioration 56 32 hallmark (90%) Very frequent (99-80%) HP:0002333
17 cherry red spot of the macula 56 32 hallmark (90%) Very frequent (99-80%) HP:0010729
18 abnormality of movement 56 32 hallmark (90%) Very frequent (99-80%) HP:0100022
19 abnormality of glycosphingolipid metabolism 56 32 hallmark (90%) Very frequent (99-80%) HP:0004343
20 macroglossia 32 HP:0000158
21 dysarthria 32 HP:0001260
22 hyperreflexia 32 HP:0001347
23 coarse facial features 32 HP:0000280
24 cardiomegaly 32 HP:0001640
25 urinary incontinence 32 HP:0000020
26 hyperhidrosis 32 HP:0000975
27 hypohidrosis 32 HP:0000966
28 impotence 32 HP:0000802
29 fasciculations 32 HP:0002380
30 hepatosplenomegaly 32 HP:0001433
31 orthostatic hypotension 32 HP:0001278
32 chronic diarrhea 32 HP:0002028
33 impaired thermal sensitivity 32 HP:0006901
34 episodic abdominal pain 32 HP:0002574
35 skeletal muscle atrophy 32 HP:0003202

MGI Mouse Phenotypes related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.26 HEXA HEXB HHEX NPC1
2 liver/biliary system MP:0005370 8.92 HEXA HEXB HHEX NPC1

Drugs & Therapeutics for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Search Clinical Trials , NIH Clinical Center for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Stem-cell-based therapeutic approaches for Sandhoff Disease, Infantile, Juvenile, and Adult Forms:
ALD-151, umbilical cord blood cells for hematologic and immunodefeciency diseases
Enriched hematopoetic stem cell for inherited metabolic disorders
Embryonic/Adult Cultured Cells Related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms:
Umbilical cord blood ALDH+ cells (ALD-151) PMIDs: 10430905
Bone marrow-derived hematopoietic stem cells (family) PMIDs: 22430083

Cochrane evidence based reviews: sandhoff disease

Genetic Tests for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Genetic tests related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms:

id Genetic test Affiliating Genes
1 Sandhoff Disease 29 24 HEXB

Anatomical Context for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

MalaCards organs/tissues related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms:

39
Brain, Spinal Cord, Eye, Liver, Spleen, Bone, Skeletal Muscle

Publications for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Variations for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

UniProtKB/Swiss-Prot genetic disease variations for Sandhoff Disease, Infantile, Juvenile, and Adult Forms:

71
id Symbol AA change Variation ID SNP ID
1 HEXB p.Ser62Leu VAR_003247 rs820878
2 HEXB p.Cys309Tyr VAR_003250
3 HEXB p.Pro417Leu VAR_003251 rs28942073
4 HEXB p.Tyr456Ser VAR_003252
5 HEXB p.Arg505Gln VAR_003253
6 HEXB p.Cys534Tyr VAR_003254
7 HEXB p.Ser255Arg VAR_011704
8 HEXB p.Pro504Ser VAR_011705
9 HEXB p.Ala543Thr VAR_011706

ClinVar genetic disease variations for Sandhoff Disease, Infantile, Juvenile, and Adult Forms:

6 (show all 21)
id Gene Variation Type Significance SNP ID Assembly Location
1 HEXB nsv513799 deletion Pathogenic
2 HEXB NM_000521.3(HEXB): c.1250C> T (p.Pro417Leu) single nucleotide variant Pathogenic/Likely pathogenic rs28942073 GRCh37 Chromosome 5, 74014629: 74014629
3 HEXB HEXB, IVS8, G-C, +5 single nucleotide variant Pathogenic
4 HEXB HEXB, 1-BP DEL, 76A deletion Pathogenic
5 HEXB NM_000521.3(HEXB): c.850C> T (p.Arg284Ter) single nucleotide variant Pathogenic rs121907986 GRCh37 Chromosome 5, 74009409: 74009409
6 HEXB HEXB, 1-BP DEL, 965T deletion Pathogenic
7 HEXB NM_000521.3(HEXB): c.115delG (p.Val39Trpfs) deletion Pathogenic rs398123443 GRCh37 Chromosome 5, 73981200: 73981200
8 HEXB NM_000521.3(HEXB): c.1238_1242delCAAAG (p.Lys414Cysfs) deletion Pathogenic rs398123445 GRCh37 Chromosome 5, 74014184: 74014188
9 HEXB NM_000521.3(HEXB): c.1243-2A> G single nucleotide variant Pathogenic rs398123446 GRCh37 Chromosome 5, 74014620: 74014620
10 HEXB NM_000521.3(HEXB): c.1375G> T (p.Asp459Tyr) single nucleotide variant Likely pathogenic rs398123447 GRCh37 Chromosome 5, 74014754: 74014754
11 HEXB NM_000521.3(HEXB): c.797A> G (p.Tyr266Cys) single nucleotide variant Likely pathogenic rs398123450 GRCh37 Chromosome 5, 74009356: 74009356
12 HEXB NM_000521.3(HEXB): c.1478T> G (p.Val493Gly) single nucleotide variant Likely pathogenic rs794727049 GRCh37 Chromosome 5, 74016313: 74016313
13 HEXB NM_000521.3(HEXB): c.1517_1529dupCAAGTGCTGTTGG (p.Glu511Lysfs) duplication Pathogenic rs797044644 GRCh37 Chromosome 5, 74016476: 74016488
14 HEXB NM_000521.3(HEXB): c.1535_1536delGA (p.Arg512Thrfs) deletion Pathogenic rs794727091 GRCh37 Chromosome 5, 74016494: 74016495
15 HEXB NM_000521.3(HEXB): c.170G> A (p.Trp57Ter) single nucleotide variant Pathogenic rs1114167287 GRCh37 Chromosome 5, 73981255: 73981255
16 HEXB NM_000521.3(HEXB): c.1023_1026delTGAG (p.Ser341Argfs) deletion Pathogenic rs886042067 GRCh37 Chromosome 5, 74011456: 74011459
17 HEXB NM_000521.3(HEXB): c.508C> T (p.Arg170Ter) single nucleotide variant Pathogenic rs753823903 GRCh37 Chromosome 5, 73989526: 73989526
18 HEXB NM_000521.3(HEXB): c.1082+5G> A single nucleotide variant Likely pathogenic rs5030731 GRCh38 Chromosome 5, 74715695: 74715695
19 HEXB NM_000521.3(HEXB): c.299G> C (p.Arg100Pro) single nucleotide variant Pathogenic rs1060499701 GRCh37 Chromosome 5, 73981384: 73981384
20 HEXB NM_000521.3(HEXB): c.778T> C (p.Tyr260His) single nucleotide variant Likely pathogenic GRCh38 Chromosome 5, 74713512: 74713512
21 HEXB NM_000521.3(HEXB): c.1597C> T (p.Arg533Cys) single nucleotide variant Pathogenic rs764552042 GRCh38 Chromosome 5, 74720731: 74720731

Copy number variations for Sandhoff Disease, Infantile, Juvenile, and Adult Forms from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 201871 5 73971603 74052869 Deletion HEXB Sandhoff disease

Expression for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Search GEO for disease gene expression data for Sandhoff Disease, Infantile, Juvenile, and Adult Forms.

Pathways for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

GO Terms for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

Cellular components related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.72 ETFA GM2A HEXA HEXB NPC1
2 azurophil granule lumen GO:0035578 9.26 GM2A HEXB
3 azurophil granule GO:0042582 9.16 HEXA HEXB
4 lysosomal lumen GO:0043202 9.13 GM2A HEXA HEXB
5 lysosome GO:0005764 8.92 GM2A HEXA HEXB NPC1

Biological processes related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.63 HEXA HEXB MGEA5
2 lipid transport GO:0006869 9.48 GM2A NPC1
3 neuromuscular process controlling balance GO:0050885 9.43 GM2A HEXB
4 lipid storage GO:0019915 9.4 GM2A HEXB
5 hyaluronan catabolic process GO:0030214 9.37 HEXA HEXB
6 chondroitin sulfate catabolic process GO:0030207 9.32 HEXA HEXB
7 keratan sulfate catabolic process GO:0042340 9.26 HEXA HEXB
8 oligosaccharide catabolic process GO:0009313 9.16 GM2A HEXB
9 ganglioside catabolic process GO:0006689 8.96 GM2A HEXB
10 glycosphingolipid metabolic process GO:0006687 8.8 GM2A HEXA HEXB

Molecular functions related to Sandhoff Disease, Infantile, Juvenile, and Adult Forms according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 lipid transporter activity GO:0005319 9.26 GM2A NPC1
2 acetylglucosaminyltransferase activity GO:0008375 9.16 HEXA HEXB
3 hydrolase activity, acting on glycosyl bonds GO:0016798 9.13 HEXA HEXB MGEA5
4 beta-N-acetylhexosaminidase activity GO:0004563 8.8 GM2A HEXA HEXB

Sources for Sandhoff Disease, Infantile, Juvenile, and Adult Forms

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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