SCHIND
MCID: SCH069
MIFTS: 36

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 71
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 73
Schind 73

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 05-Mar-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, cerebellum and spinal cord, 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 05-Mar-2021)

UniProtKB/Swiss-Prot : 73 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 11.4
4 neurodegeneration with brain iron accumulation 2a 10.2
5 neuroaxonal dystrophy 10.2
6 angiokeratoma 10.1
7 inherited metabolic disorder 10.0
8 demyelinating polyneuropathy 10.0
9 polyneuropathy 10.0
10 sensorineural hearing loss 10.0
11 autosomal recessive disease 10.0
12 autism 10.0
13 carpal tunnel syndrome 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 05-Mar-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 05-Mar-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, Cerebellum, Spinal Cord

Publications for Schindler Disease, Type I

Articles related to Schindler Disease, Type I:

# Title Authors PMID Year
1
Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: no association with neuroaxonal dystrophy? 6 57
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. 6 57
8071745 1994
4
Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy. 57 6
2243144 1990
5
Neuroaxonal dystrophy in infantile alpha-N-acetylgalactosaminidase deficiency. 57
8523030 1995
6
Molecular cloning of two species of cDNAs for human alpha-N-acetylgalactosaminidase and expression in mammalian cells. 6
2372288 1990
7
Neuroaxonal dystrophy due to lysosomal alpha-N-acetylgalactosaminidase deficiency. 57
2733734 1989
8
alpha-N-acetylgalactosaminidase deficiency, a new lysosomal storage disorder. 57
3149698 1988
9
Lysosomal alpha-N-acetylgalactosaminidase deficiency: a new inherited metabolic disease. 57
2889023 1987
10
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 79)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NAGA NM_000262.3(NAGA):c.479C>G (p.Ser160Cys) SNV Pathogenic 18165 rs121434532 22:42463140-42463140 22:42067136-42067136
2 NAGA NM_000262.3(NAGA):c.443G>A (p.Trp148Ter) SNV Pathogenic 947187 22:42463176-42463176 22:42067172-42067172
3 NAGA NM_000262.3(NAGA):c.973G>A (p.Glu325Lys) SNV Pathogenic/Likely pathogenic 18162 rs121434529 22:42457056-42457056 22:42061052-42061052
4 NAGA NM_000262.3(NAGA):c.324+1G>A SNV Likely pathogenic 566309 rs140673721 22:42463768-42463768 22:42067764-42067764
5 NAGA NM_000262.3(NAGA):c.606C>A (p.Tyr202Ter) SNV Likely pathogenic 212736 rs779423223 22:42461895-42461895 22:42065891-42065891
6 NAGA NM_000262.3(NAGA):c.479C>G (p.Ser160Cys) SNV Conflicting interpretations of pathogenicity 18165 rs121434532 22:42463140-42463140 22:42067136-42067136
7 NAGA NM_000262.3(NAGA):c.406G>A (p.Asp136Asn) SNV Conflicting interpretations of pathogenicity 341911 rs186173534 22:42463213-42463213 22:42067209-42067209
8 NAGA NM_000262.3(NAGA):c.973G>A (p.Glu325Lys) SNV Conflicting interpretations of pathogenicity 18162 rs121434529 22:42457056-42457056 22:42061052-42061052
9 NAGA NM_000262.3(NAGA):c.280G>A (p.Asp94Asn) SNV Conflicting interpretations of pathogenicity 341912 rs73167107 22:42463813-42463813 22:42067809-42067809
10 NAGA NM_000262.3(NAGA):c.993G>T (p.Leu331=) SNV Conflicting interpretations of pathogenicity 341905 rs147853281 22:42457036-42457036 22:42061032-42061032
11 WBP2NL NM_000262.3(NAGA):c.*1299C>T SNV Uncertain significance 341892 rs886057592 22:42454984-42454984 22:42058980-42058980
12 WBP2NL NM_000262.3(NAGA):c.*1252T>C SNV Uncertain significance 341893 rs886057593 22:42455031-42455031 22:42059027-42059027
13 NAGA NM_000262.3(NAGA):c.*155A>G SNV Uncertain significance 341901 rs761125179 22:42456128-42456128 22:42060124-42060124
14 NAGA NM_000262.3(NAGA):c.859C>T (p.Arg287Cys) SNV Uncertain significance 341907 rs368220690 22:42458929-42458929 22:42062925-42062925
15 WBP2NL NM_000262.3(NAGA):c.*1789del Deletion Uncertain significance 341887 rs10713176 22:42454494-42454494 22:42058490-42058490
16 WBP2NL NM_000262.3(NAGA):c.*926C>G SNV Uncertain significance 341896 rs886057595 22:42455357-42455357 22:42059353-42059353
17 NAGA NM_000262.3(NAGA):c.-306C>A SNV Uncertain significance 341918 rs886057598 22:42466607-42466607 22:42070603-42070603
18 NAGA NM_000262.3(NAGA):c.-502A>C SNV Uncertain significance 341920 rs886057600 22:42466803-42466803 22:42070799-42070799
19 NAGA NM_000262.3(NAGA):c.*176C>G SNV Uncertain significance 341899 rs191051580 22:42456107-42456107 22:42060103-42060103
20 NAGA NM_000262.3(NAGA):c.1013T>C (p.Leu338Ser) SNV Uncertain significance 341904 rs778343270 22:42457016-42457016 22:42061012-42061012
21 NAGA NM_000262.3(NAGA):c.549C>T (p.Ile183=) SNV Uncertain significance 341910 rs374984089 22:42462762-42462762 22:42066758-42066758
22 NAGA NM_000262.3(NAGA):c.110G>A (p.Arg37His) SNV Uncertain significance 341913 rs199834981 22:42464485-42464485 22:42068481-42068481
23 NAGA NM_000262.3(NAGA):c.19C>T (p.Leu7Phe) SNV Uncertain significance 341915 rs886057597 22:42464576-42464576 22:42068572-42068572
24 WBP2NL NM_000262.3(NAGA):c.*1090G>A SNV Uncertain significance 341894 rs886057594 22:42455193-42455193 22:42059189-42059189
25 WBP2NL NM_000262.3(NAGA):c.*1501C>G SNV Uncertain significance 341890 rs750373836 22:42454782-42454782 22:42058778-42058778
26 NAGA NM_000262.3(NAGA):c.*268G>A SNV Uncertain significance 341898 rs886057596 22:42456015-42456015 22:42060011-42060011
27 NAGA NM_000262.3(NAGA):c.-496G>C SNV Uncertain significance 341919 rs886057599 22:42466797-42466797 22:42070793-42070793
28 NAGA NM_000262.3(NAGA):c.1142G>A (p.Arg381Gln) SNV Uncertain significance 566550 rs144771084 22:42456377-42456377 22:42060373-42060373
29 NAGA NM_000262.3(NAGA):c.1225T>A (p.Ser409Thr) SNV Uncertain significance 576897 rs1569456853 22:42456294-42456294 22:42060290-42060290
30 NAGA NM_000262.3(NAGA):c.280G>A (p.Asp94Asn) SNV Uncertain significance 341912 rs73167107 22:42463813-42463813 22:42067809-42067809
31 NAGA NM_000262.3(NAGA):c.16G>A (p.Val6Met) SNV Uncertain significance 643747 rs1602499597 22:42466286-42466286 22:42070282-42070282
32 NAGA NM_000262.3(NAGA):c.406G>C (p.Asp136His) SNV Uncertain significance 658016 rs186173534 22:42463213-42463213 22:42067209-42067209
33 NAGA NM_000262.3(NAGA):c.487G>A (p.Glu163Lys) SNV Uncertain significance 660319 rs372458856 22:42463132-42463132 22:42067128-42067128
34 NAGA NM_000262.3(NAGA):c.833C>T (p.Ala278Val) SNV Uncertain significance 840249 22:42458955-42458955 22:42062951-42062951
35 NAGA NM_000262.3(NAGA):c.582C>T (p.Gly194=) SNV Uncertain significance 899381 22:42462729-42462729 22:42066725-42066725
36 NAGA NM_000262.3(NAGA):c.493C>T (p.Arg165Trp) SNV Uncertain significance 899382 22:42463126-42463126 22:42067122-42067122
37 NAGA NM_000262.3(NAGA):c.486C>G (p.Pro162=) SNV Uncertain significance 899383 22:42463133-42463133 22:42067129-42067129
38 NAGA NM_000262.3(NAGA):c.-43C>T SNV Uncertain significance 341916 rs753592199 22:42466344-42466344 22:42070340-42070340
39 NAGA NM_000262.3(NAGA):c.638G>A (p.Arg213His) SNV Uncertain significance 341909 rs781499383 22:42461863-42461863 22:42065859-42065859
40 WBP2NL NM_000262.3(NAGA):c.*1484A>G SNV Uncertain significance 900326 22:42454799-42454799 22:42058795-42058795
41 NAGA NM_000262.3(NAGA):c.*107G>A SNV Uncertain significance 900386 22:42456176-42456176 22:42060172-42060172
42 NAGA NM_000262.3(NAGA):c.*55C>T SNV Uncertain significance 900446 22:42456228-42456228 22:42060224-42060224
43 NAGA NM_000262.3(NAGA):c.1209C>T (p.Ile403=) SNV Uncertain significance 719610 rs201582948 22:42456310-42456310 22:42060306-42060306
44 NAGA NM_000262.3(NAGA):c.324C>T (p.Tyr108=) SNV Uncertain significance 900504 22:42463769-42463769 22:42067765-42067765
45 WBP2NL NM_000262.3(NAGA):c.*1862C>A SNV Uncertain significance 901975 22:42454421-42454421 22:42058417-42058417
46 NAGA NM_000262.3(NAGA):c.*730T>C SNV Uncertain significance 902053 22:42455553-42455553 22:42059549-42059549
47 NAGA NM_000262.3(NAGA):c.*572G>A SNV Uncertain significance 902054 22:42455711-42455711 22:42059707-42059707
48 WBP2NL NM_000262.3(NAGA):c.*1724C>G SNV Uncertain significance 902876 22:42454559-42454559 22:42058555-42058555
49 WBP2NL NM_000262.3(NAGA):c.*1555C>T SNV Uncertain significance 900325 22:42454728-42454728 22:42058724-42058724
50 NAGA NM_000262.3(NAGA):c.697G>A (p.Val233Met) SNV Uncertain significance 902999 22:42461804-42461804 22:42065800-42065800

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

73
# 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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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