SCHIND
MCID: SCH069
MIFTS: 37

Schindler Disease, Type I (SCHIND)

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

Aliases & Classifications for Schindler Disease, Type I

MalaCards integrated aliases for Schindler Disease, Type I:

Name: Schindler Disease, Type I 57 13 70
Alpha-N-Acetylgalactosaminidase Deficiency Type 1 58 29 6
Neuroaxonal Dystrophy, Schindler Type 57 20
Schindler Disease Type 1 20 58
Alpha-N-Acetylgalactosaminidase Deficiency, Type I 57
Alpha-N-Acetylgalactosaminidase Deficiency, Type 1 20
Alpha-N-Acetylgalactosaminidase Deficiency Type 3 58
Schindler Disease, Type Iii 57
Schindler Disease, Type 3 6
Schindler Disease, Type 1 39
Schindler Disease Type 3 58
Schindler Disease Type I 20
Naga Deficiency, Type I 57
Naga Deficiency, Type 1 20
Naga Deficiency Type 3 58
Naga Deficiency Type 1 58
Schindler Disease 72
Schind 72

Characteristics:

Orphanet epidemiological data:

58
alpha-n-acetylgalactosaminidase deficiency type 1
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
alpha-n-acetylgalactosaminidase deficiency type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
three main phenotypes
type i is infantile-onset, severe
type ii is adult-onset (kanzaki disease, )
type iii is intermediate form
type i onset at 8 to 15 months of age after normal development
type i has most severe manifestations by age 4-5 years


HPO:

31
schindler disease, type i:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


Summaries for Schindler Disease, Type I

GARD : 20 Schindler disease is an inherited condition that primarily causes neurological problems. There are three types of Schindler disease. Schindler disease type 1, also called the infantile type, is the most severe form. Babies with this condition appear healthy a birth, but by the age of 8 to 15 months they stop developing new skills and begin losing skills they had already acquired. As the condition progresses, affected individuals develop blindness and seizures, and eventually lose awareness of their surroundings and become unresponsive. People with this form of the condition usually don't survive past early childhood. Schindler disease type 1 is caused by mutations in the NAGA gene. The condition follows an autosomal recessive pattern of inheritance.

MalaCards based summary : Schindler Disease, Type I, also known as alpha-n-acetylgalactosaminidase deficiency type 1, is related to schindler disease and n-acetyl-alpha-d-galactosaminidase deficiency type iii, and has symptoms including seizures, myoclonus and muscle spasticity. An important gene associated with Schindler Disease, Type I is NAGA (Alpha-N-Acetylgalactosaminidase). Affiliated tissues include eye, liver and cerebellum, and related phenotypes are spasticity and abnormal pyramidal sign

OMIM® : 57 Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder. It is clinically heterogeneous with 3 main phenotypes: type I is an infantile-onset neuroaxonal dystrophy; type II, also known as Kanzaki disease (609242), is an adult-onset disorder characterized by angiokeratoma corporis diffusum and mild intellectual impairment; and type III is an intermediate disorder with mild to moderate neurologic manifestations (Desnick and Schindler, 2001). (609241) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 Schindler disease: Form of NAGA deficiency characterized by early-onset neuroaxonal dystrophy and neurological signs (convulsion during fever, epilepsy, psychomotor retardation and hypotonia). NAGA deficiency is typically classified in three main phenotypes: NAGA deficiency type I (Schindler disease or Schindler disease type I) with severe manifestations; NAGA deficiency type II (Kanzazi disease or Schindler disease type II) which is mild; NAGA deficiency type III (Schindler disease type III) characterized by mild-to-moderate neurologic manifestations. NAGA deficiency results in the increased urinary excretion of glycopeptides and oligosaccharides containing alpha-N-acetylgalactosaminyl moieties. Inheritance is autosomal recessive.

Related Diseases for Schindler Disease, Type I

Diseases in the Schindler Disease family:

Schindler Disease, Type I

Diseases related to Schindler Disease, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 schindler disease 11.6
2 n-acetyl-alpha-d-galactosaminidase deficiency type iii 11.5
3 kanzaki disease 11.5
4 neurodegeneration with brain iron accumulation 2a 10.2
5 neuroaxonal dystrophy 10.2
6 angiokeratoma 10.1
7 carpal tunnel syndrome 10.0
8 autism 10.0
9 autosomal recessive disease 10.0
10 sensorineural hearing loss 10.0
11 polyneuropathy 10.0
12 demyelinating polyneuropathy 10.0
13 inherited metabolic disorder 10.0

Graphical network of the top 20 diseases related to Schindler Disease, Type I:



Diseases related to Schindler Disease, Type I

Symptoms & Phenotypes for Schindler Disease, Type I

Human phenotypes related to Schindler Disease, Type I:

58 31 (show all 38)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
2 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
3 muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001324
4 developmental regression 58 31 hallmark (90%) Very frequent (99-80%) HP:0002376
5 hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000365
6 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001263
7 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
8 generalized amyotrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003700
9 cerebral visual impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0100704
10 abnormality of brainstem morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0002363
11 seizure 31 hallmark (90%) HP:0001250
12 hypotonia 31 hallmark (90%) HP:0001252
13 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
14 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
15 hyperkeratosis 58 31 frequent (33%) Frequent (79-30%) HP:0000962
16 myoclonus 58 31 frequent (33%) Frequent (79-30%) HP:0001336
17 strabismus 58 31 frequent (33%) Frequent (79-30%),Very frequent (99-80%) HP:0000486
18 autism 58 31 frequent (33%) Frequent (79-30%),Very frequent (99-80%) HP:0000717
19 hemiplegia/hemiparesis 58 31 frequent (33%) Frequent (79-30%) HP:0004374
20 vertigo 58 31 frequent (33%) Frequent (79-30%) HP:0002321
21 telangiectasia of the skin 58 31 frequent (33%) Frequent (79-30%) HP:0100585
22 abnormality of extrapyramidal motor function 58 31 frequent (33%) Frequent (79-30%) HP:0002071
23 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0002240
24 lymphedema 58 31 occasional (7.5%) Occasional (29-5%) HP:0001004
25 hypertrophic cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0001639
26 aplasia/hypoplasia of the cerebellum 58 31 occasional (7.5%) Occasional (29-5%) HP:0007360
27 paresthesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003401
28 intellectual disability 58 Very frequent (99-80%)
29 seizures 58 Very frequent (99-80%),Very frequent (99-80%)
30 hyperreflexia 31 HP:0001347
31 osteopenia 31 HP:0000938
32 muscular hypotonia 58 Very frequent (99-80%)
33 cataract 58 Very frequent (99-80%)
34 increased urinary o-linked sialopeptides 31 HP:0003461
35 sensory neuropathy 58 Frequent (79-30%)
36 peripheral neuropathy 58 Occasional (29-5%)
37 generalized hypotonia 31 HP:0001290
38 telangiectasia 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
myoclonus
unresponsive to stimuli
more
Skeletal:
osteopenia
limb contractures by age 4-5 years

Muscle Soft Tissue:
muscular atrophy, generalized

Head And Neck Eyes:
nystagmus
optic atrophy
strabismus
cortical blindness

Laboratory Abnormalities:
increased urinary o-linked sialopeptides
lack of lysosomal inclusions in visceral organs
decreased alpha-n-acetylgalactosaminidase protein
decreased alpha-n-acetylgalactosaminidase activity (less than 2% of control)
increased urinary oligosaccharides

Clinical features from OMIM®:

609241 (Updated 20-May-2021)

UMLS symptoms related to Schindler Disease, Type I:


seizures; myoclonus; muscle spasticity; unresponsive to stimuli

Drugs & Therapeutics for Schindler Disease, Type I

Search Clinical Trials , NIH Clinical Center for Schindler Disease, Type I

Genetic Tests for Schindler Disease, Type I

Genetic tests related to Schindler Disease, Type I:

# Genetic test Affiliating Genes
1 Alpha-N-Acetylgalactosaminidase Deficiency Type 1 29 NAGA

Anatomical Context for Schindler Disease, Type I

MalaCards organs/tissues related to Schindler Disease, Type I:

40
Eye, Liver, Cerebellum, Spinal Cord, Brain

Publications for Schindler Disease, Type I

Articles related to Schindler Disease, Type I:

(show all 14)
# Title Authors PMID Year
1
Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: no association with neuroaxonal dystrophy? 57 6
11313741 2001
2
Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype. 57 6
8782044 1996
3
alpha-N-acetylgalactosaminidase deficiency with mild clinical manifestations and difficult biochemical diagnosis. 57 6
8071745 1994
4
Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy. 6 57
2243144 1990
5
A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Ménière's syndrome and without mental retardation. 6
11251574 2001
6
Neuroaxonal dystrophy in infantile alpha-N-acetylgalactosaminidase deficiency. 57
8523030 1995
7
The molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes angiokeratoma corporis diffusum with glycopeptiduria. 6
8040340 1994
8
Mild phenotypic expression of alpha-N-acetylgalactosaminidase deficiency in two adult siblings. 6
7707696 1994
9
Molecular cloning of two species of cDNAs for human alpha-N-acetylgalactosaminidase and expression in mammalian cells. 6
2372288 1990
10
Neuroaxonal dystrophy due to lysosomal alpha-N-acetylgalactosaminidase deficiency. 57
2733734 1989
11
alpha-N-acetylgalactosaminidase deficiency, a new lysosomal storage disorder. 57
3149698 1988
12
Lysosomal alpha-N-acetylgalactosaminidase deficiency: a new inherited metabolic disease. 57
2889023 1987
13
An interaction model of a Poisson and a renewal process related to neuron firing. 6
1131374 1975
14
Automated chip-nanoelectrospray mass spectrometry for glycourinomics in Schindler disease type I. 61
25243357 2014

Variations for Schindler Disease, Type I

ClinVar genetic disease variations for Schindler Disease, Type I:

6 (show top 50) (show all 84)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NAGA NM_000262.3(NAGA):c.479C>G (p.Ser160Cys) SNV Pathogenic 18165 rs121434532 GRCh37: 22:42463140-42463140
GRCh38: 22:42067136-42067136
2 NAGA NM_000262.3(NAGA):c.443G>A (p.Trp148Ter) SNV Pathogenic 947187 GRCh37: 22:42463176-42463176
GRCh38: 22:42067172-42067172
3 NAGA NM_000262.3(NAGA):c.973G>A (p.Glu325Lys) SNV Pathogenic/Likely pathogenic 18162 rs121434529 GRCh37: 22:42457056-42457056
GRCh38: 22:42061052-42061052
4 NAGA NM_000262.3(NAGA):c.324+1G>A SNV Likely pathogenic 566309 rs140673721 GRCh37: 22:42463768-42463768
GRCh38: 22:42067764-42067764
5 NAGA NM_000262.3(NAGA):c.606C>A (p.Tyr202Ter) SNV Likely pathogenic 212736 rs779423223 GRCh37: 22:42461895-42461895
GRCh38: 22:42065891-42065891
6 NAGA NM_000262.3(NAGA):c.479C>G (p.Ser160Cys) SNV Conflicting interpretations of pathogenicity 18165 rs121434532 GRCh37: 22:42463140-42463140
GRCh38: 22:42067136-42067136
7 NAGA NM_000262.3(NAGA):c.406G>A (p.Asp136Asn) SNV Conflicting interpretations of pathogenicity 341911 rs186173534 GRCh37: 22:42463213-42463213
GRCh38: 22:42067209-42067209
8 NAGA NM_000262.3(NAGA):c.973G>A (p.Glu325Lys) SNV Conflicting interpretations of pathogenicity 18162 rs121434529 GRCh37: 22:42457056-42457056
GRCh38: 22:42061052-42061052
9 NAGA NM_000262.3(NAGA):c.280G>A (p.Asp94Asn) SNV Conflicting interpretations of pathogenicity 341912 rs73167107 GRCh37: 22:42463813-42463813
GRCh38: 22:42067809-42067809
10 NAGA NM_000262.3(NAGA):c.993G>T (p.Leu331=) SNV Conflicting interpretations of pathogenicity 341905 rs147853281 GRCh37: 22:42457036-42457036
GRCh38: 22:42061032-42061032
11 WBP2NL , NAGA NM_000262.3(NAGA):c.*1299C>T SNV Uncertain significance 341892 rs886057592 GRCh37: 22:42454984-42454984
GRCh38: 22:42058980-42058980
12 WBP2NL , NAGA NM_000262.3(NAGA):c.*1252T>C SNV Uncertain significance 341893 rs886057593 GRCh37: 22:42455031-42455031
GRCh38: 22:42059027-42059027
13 NAGA NM_000262.3(NAGA):c.*155A>G SNV Uncertain significance 341901 rs761125179 GRCh37: 22:42456128-42456128
GRCh38: 22:42060124-42060124
14 NAGA NM_000262.3(NAGA):c.859C>T (p.Arg287Cys) SNV Uncertain significance 341907 rs368220690 GRCh37: 22:42458929-42458929
GRCh38: 22:42062925-42062925
15 WBP2NL , NAGA NM_000262.3(NAGA):c.*1789del Deletion Uncertain significance 341887 rs10713176 GRCh37: 22:42454494-42454494
GRCh38: 22:42058490-42058490
16 WBP2NL , NAGA NM_000262.3(NAGA):c.*926C>G SNV Uncertain significance 341896 rs886057595 GRCh37: 22:42455357-42455357
GRCh38: 22:42059353-42059353
17 NAGA NM_000262.3(NAGA):c.-306C>A SNV Uncertain significance 341918 rs886057598 GRCh37: 22:42466607-42466607
GRCh38: 22:42070603-42070603
18 NAGA NM_000262.3(NAGA):c.-502A>C SNV Uncertain significance 341920 rs886057600 GRCh37: 22:42466803-42466803
GRCh38: 22:42070799-42070799
19 NAGA NM_000262.3(NAGA):c.*176C>G SNV Uncertain significance 341899 rs191051580 GRCh37: 22:42456107-42456107
GRCh38: 22:42060103-42060103
20 NAGA NM_000262.3(NAGA):c.1013T>C (p.Leu338Ser) SNV Uncertain significance 341904 rs778343270 GRCh37: 22:42457016-42457016
GRCh38: 22:42061012-42061012
21 NAGA NM_000262.3(NAGA):c.549C>T (p.Ile183=) SNV Uncertain significance 341910 rs374984089 GRCh37: 22:42462762-42462762
GRCh38: 22:42066758-42066758
22 NAGA NM_000262.3(NAGA):c.110G>A (p.Arg37His) SNV Uncertain significance 341913 rs199834981 GRCh37: 22:42464485-42464485
GRCh38: 22:42068481-42068481
23 NAGA NM_000262.3(NAGA):c.19C>T (p.Leu7Phe) SNV Uncertain significance 341915 rs886057597 GRCh37: 22:42464576-42464576
GRCh38: 22:42068572-42068572
24 WBP2NL , NAGA NM_000262.3(NAGA):c.*1090G>A SNV Uncertain significance 341894 rs886057594 GRCh37: 22:42455193-42455193
GRCh38: 22:42059189-42059189
25 WBP2NL , NAGA NM_000262.3(NAGA):c.*1501C>G SNV Uncertain significance 341890 rs750373836 GRCh37: 22:42454782-42454782
GRCh38: 22:42058778-42058778
26 NAGA NM_000262.3(NAGA):c.*268G>A SNV Uncertain significance 341898 rs886057596 GRCh37: 22:42456015-42456015
GRCh38: 22:42060011-42060011
27 NAGA NM_000262.3(NAGA):c.-496G>C SNV Uncertain significance 341919 rs886057599 GRCh37: 22:42466797-42466797
GRCh38: 22:42070793-42070793
28 NAGA NM_000262.3(NAGA):c.1142G>A (p.Arg381Gln) SNV Uncertain significance 566550 rs144771084 GRCh37: 22:42456377-42456377
GRCh38: 22:42060373-42060373
29 NAGA NM_000262.3(NAGA):c.1225T>A (p.Ser409Thr) SNV Uncertain significance 576897 rs1569456853 GRCh37: 22:42456294-42456294
GRCh38: 22:42060290-42060290
30 NAGA NM_000262.3(NAGA):c.280G>A (p.Asp94Asn) SNV Uncertain significance 341912 rs73167107 GRCh37: 22:42463813-42463813
GRCh38: 22:42067809-42067809
31 NAGA NM_000262.3(NAGA):c.16G>A (p.Val6Met) SNV Uncertain significance 643747 rs1602499597 GRCh37: 22:42466286-42466286
GRCh38: 22:42070282-42070282
32 NAGA NM_000262.3(NAGA):c.406G>C (p.Asp136His) SNV Uncertain significance 658016 rs186173534 GRCh37: 22:42463213-42463213
GRCh38: 22:42067209-42067209
33 NAGA NM_000262.3(NAGA):c.487G>A (p.Glu163Lys) SNV Uncertain significance 660319 rs372458856 GRCh37: 22:42463132-42463132
GRCh38: 22:42067128-42067128
34 NAGA NM_000262.3(NAGA):c.833C>T (p.Ala278Val) SNV Uncertain significance 840249 GRCh37: 22:42458955-42458955
GRCh38: 22:42062951-42062951
35 NAGA NM_000262.3(NAGA):c.582C>T (p.Gly194=) SNV Uncertain significance 899381 GRCh37: 22:42462729-42462729
GRCh38: 22:42066725-42066725
36 NAGA NM_000262.3(NAGA):c.493C>T (p.Arg165Trp) SNV Uncertain significance 899382 GRCh37: 22:42463126-42463126
GRCh38: 22:42067122-42067122
37 NAGA NM_000262.3(NAGA):c.486C>G (p.Pro162=) SNV Uncertain significance 899383 GRCh37: 22:42463133-42463133
GRCh38: 22:42067129-42067129
38 NAGA NM_000262.3(NAGA):c.-43C>T SNV Uncertain significance 341916 rs753592199 GRCh37: 22:42466344-42466344
GRCh38: 22:42070340-42070340
39 NAGA NM_000262.3(NAGA):c.638G>A (p.Arg213His) SNV Uncertain significance 341909 rs781499383 GRCh37: 22:42461863-42461863
GRCh38: 22:42065859-42065859
40 WBP2NL , NAGA NM_000262.3(NAGA):c.*1484A>G SNV Uncertain significance 900326 GRCh37: 22:42454799-42454799
GRCh38: 22:42058795-42058795
41 NAGA NM_000262.3(NAGA):c.104G>A (p.Arg35His) SNV Uncertain significance 1000987 GRCh37: 22:42464491-42464491
GRCh38: 22:42068487-42068487
42 NAGA NM_000262.3(NAGA):c.358G>A (p.Ala120Thr) SNV Uncertain significance 218437 rs749506008 GRCh37: 22:42463261-42463261
GRCh38: 22:42067257-42067257
43 NAGA NM_000262.3(NAGA):c.983T>C (p.Met328Thr) SNV Uncertain significance 596276 rs140356002 GRCh37: 22:42457046-42457046
GRCh38: 22:42061042-42061042
44 NAGA NM_000262.3(NAGA):c.1224_1225insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAGATCGAGACCACGGTGAAACNNNNNNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACCTGGAGATG (p.Ser409fs) Insertion Uncertain significance 1016714 GRCh37: 22:42456294-42456295
GRCh38: 22:42060290-42060291
45 NAGA NM_000262.3(NAGA):c.230T>C (p.Ile77Thr) SNV Uncertain significance 1043247 GRCh37: 22:42463863-42463863
GRCh38: 22:42067859-42067859
46 NAGA NM_000262.3(NAGA):c.*107G>A SNV Uncertain significance 900386 GRCh37: 22:42456176-42456176
GRCh38: 22:42060172-42060172
47 NAGA NM_000262.3(NAGA):c.*55C>T SNV Uncertain significance 900446 GRCh37: 22:42456228-42456228
GRCh38: 22:42060224-42060224
48 NAGA NM_000262.3(NAGA):c.1209C>T (p.Ile403=) SNV Uncertain significance 719610 rs201582948 GRCh37: 22:42456310-42456310
GRCh38: 22:42060306-42060306
49 NAGA NM_000262.3(NAGA):c.324C>T (p.Tyr108=) SNV Uncertain significance 900504 GRCh37: 22:42463769-42463769
GRCh38: 22:42067765-42067765
50 WBP2NL , NAGA NM_000262.3(NAGA):c.*1862C>A SNV Uncertain significance 901975 GRCh37: 22:42454421-42454421
GRCh38: 22:42058417-42058417

UniProtKB/Swiss-Prot genetic disease variations for Schindler Disease, Type I:

72
# Symbol AA change Variation ID SNP ID
1 NAGA p.Ser160Cys VAR_000496 rs121434532
2 NAGA p.Glu325Lys VAR_000497 rs121434529

Expression for Schindler Disease, Type I

Search GEO for disease gene expression data for Schindler Disease, Type I.

Pathways for Schindler Disease, Type I

GO Terms for Schindler Disease, Type I

Sources for Schindler Disease, Type I

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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