SCHIND
MCID: SCH069
MIFTS: 36

Schindler Disease, Type I (SCHIND)

Categories: 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 72
Schindler Disease, Type 1 29 6 40
Neuroaxonal Dystrophy, Schindler Type 57 53
Schindler Disease Type 1 53 59
Alpha-N-Acetylgalactosaminidase Deficiency, Type I 57
Alpha-N-Acetylgalactosaminidase Deficiency, Type 1 53
Alpha-N-Acetylgalactosaminidase Deficiency Type 3 59
Alpha-N-Acetylgalactosaminidase Deficiency Type 1 59
Schindler Disease, Type Iii 57
Schindler Disease, Type 3 6
Schindler Disease Type 3 59
Schindler Disease Type I 53
Naga Deficiency, Type I 57
Naga Deficiency, Type 1 53
Naga Deficiency Type 3 59
Naga Deficiency Type 1 59
Schindler Disease 74
Schind 74

Characteristics:

Orphanet epidemiological data:

59
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
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:

32
schindler disease, type i:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

OMIM 57 609241
ICD10 via Orphanet 34 E77.1
UMLS via Orphanet 73 C1836544 C1836545
UMLS 72 C1836544

Summaries for Schindler Disease, Type I

NIH Rare Diseases : 53 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 schindler disease, type 1, is related to schindler disease and kanzaki disease, and has symptoms including seizures, myoclonus and muscle spasticity. An important gene associated with Schindler Disease, Type I is NAGA (Alpha-N-Acetylgalactosaminidase). The drug polysaccharide-K has been mentioned in the context of this disorder. Affiliated tissues include cerebellum, skin and eye, and related phenotypes are intellectual disability and seizures

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)

UniProtKB/Swiss-Prot : 74 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:

# Related Disease Score Top Affiliating Genes
1 schindler disease 12.3
2 kanzaki disease 12.0
3 n-acetyl-alpha-d-galactosaminidase deficiency type iii 11.8
4 neurodegeneration with brain iron accumulation 2a 10.3
5 neuroaxonal dystrophy 10.3
6 autism 10.1
7 fabry disease 10.1
8 autosomal recessive disease 10.1
9 angiokeratoma 10.1
10 inherited metabolic disorder 10.1

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:

59 32 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
2 seizures 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001250
3 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
4 spasticity 59 32 hallmark (90%) Very frequent (99-80%) HP:0001257
5 muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0001324
6 developmental regression 59 32 hallmark (90%) Very frequent (99-80%) HP:0002376
7 abnormal pyramidal sign 59 32 hallmark (90%) Very frequent (99-80%) HP:0007256
8 hearing impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000365
9 cataract 59 32 hallmark (90%) Very frequent (99-80%) HP:0000518
10 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001263
11 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
12 strabismus 59 32 frequent (33%) Frequent (79-30%),Very frequent (99-80%) HP:0000486
13 autism 59 32 frequent (33%) Frequent (79-30%),Very frequent (99-80%) HP:0000717
14 abnormality of brainstem morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0002363
15 generalized amyotrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0003700
16 cerebral visual impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0100704
17 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
18 hepatomegaly 59 32 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0002240
19 optic atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0000648
20 hypertrophic cardiomyopathy 59 32 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0001639
21 hyperkeratosis 59 32 frequent (33%) Frequent (79-30%) HP:0000962
22 telangiectasia of the skin 59 32 frequent (33%) Frequent (79-30%) HP:0100585
23 hemiplegia/hemiparesis 59 32 frequent (33%) Frequent (79-30%) HP:0004374
24 myoclonus 59 32 frequent (33%) Frequent (79-30%) HP:0001336
25 vertigo 59 32 frequent (33%) Frequent (79-30%) HP:0002321
26 abnormality of extrapyramidal motor function 59 32 frequent (33%) Frequent (79-30%) HP:0002071
27 lymphedema 59 32 occasional (7.5%) Occasional (29-5%) HP:0001004
28 paresthesia 59 32 occasional (7.5%) Occasional (29-5%) HP:0003401
29 aplasia/hypoplasia of the cerebellum 59 32 occasional (7.5%) Occasional (29-5%) HP:0007360
30 osteopenia 32 HP:0000938
31 hyperreflexia 32 HP:0001347
32 generalized hypotonia 32 HP:0001290
33 sensory neuropathy 59 Frequent (79-30%)
34 peripheral neuropathy 59 Occasional (29-5%)
35 increased urinary o-linked sialopeptides 32 HP:0003461
36 telangiectasia 59 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
optic atrophy
strabismus
cortical blindness

Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
myoclonus
unresponsive to stimuli
more
Muscle Soft Tissue:
muscular atrophy, generalized

Skeletal:
osteopenia
limb contractures by age 4-5 years

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

UMLS symptoms related to Schindler Disease, Type I:


seizures, myoclonus, muscle spasticity, unresponsive to stimuli

Drugs & Therapeutics for Schindler Disease, Type I

Drugs for Schindler Disease, Type I (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 polysaccharide-K

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Longitudinal Studies of the Glycoproteinoses Unknown status NCT01891422

Search 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 Schindler Disease, Type 1 29 NAGA

Anatomical Context for Schindler Disease, Type I

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

41
Cerebellum, Skin, Eye, 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? 8 71
11313741 2001
2
Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype. 8 71
8782044 1996
3
alpha-N-acetylgalactosaminidase deficiency with mild clinical manifestations and difficult biochemical diagnosis. 8 71
8071745 1994
4
Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy. 8 71
2243144 1990
5
Neuroaxonal dystrophy in infantile alpha-N-acetylgalactosaminidase deficiency. 8
8523030 1995
6
Molecular cloning of two species of cDNAs for human alpha-N-acetylgalactosaminidase and expression in mammalian cells. 71
2372288 1990
7
Neuroaxonal dystrophy due to lysosomal alpha-N-acetylgalactosaminidase deficiency. 8
2733734 1989
8
alpha-N-acetylgalactosaminidase deficiency, a new lysosomal storage disorder. 8
3149698 1988
9
Lysosomal alpha-N-acetylgalactosaminidase deficiency: a new inherited metabolic disease. 8
2889023 1987
10
Automated chip-nanoelectrospray mass spectrometry for glycourinomics in Schindler disease type I. 38
25243357 2014

Variations for Schindler Disease, Type I

ClinVar genetic disease variations for Schindler Disease, Type I:

6 (show all 48)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 NAGA NM_000262.3(NAGA): c.973G> A (p.Glu325Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121434529 22:42457056-42457056 22:42061052-42061052
2 NAGA NM_000262.3(NAGA): c.479C> G (p.Ser160Cys) single nucleotide variant Likely pathogenic rs121434532 22:42463140-42463140 22:42067136-42067136
3 NAGA NM_000262.3(NAGA): c.606C> A (p.Tyr202Ter) single nucleotide variant Likely pathogenic rs779423223 22:42461895-42461895 22:42065891-42065891
4 NAGA NM_000262.3(NAGA): c.324+1G> A single nucleotide variant Likely pathogenic 22:42463768-42463768 22:42067764-42067764
5 NAGA NM_000262.3(NAGA): c.1225T> A (p.Ser409Thr) single nucleotide variant Uncertain significance 22:42456294-42456294 22:42060290-42060290
6 NAGA NM_000262.3(NAGA): c.1142G> A (p.Arg381Gln) single nucleotide variant Uncertain significance 22:42456377-42456377 22:42060373-42060373
7 NAGA NM_000262.3(NAGA): c.487G> A (p.Glu163Lys) single nucleotide variant Uncertain significance 22:42463132-42463132 22:42067128-42067128
8 NAGA NM_000262.3(NAGA): c.406G> C (p.Asp136His) single nucleotide variant Uncertain significance 22:42463213-42463213 22:42067209-42067209
9 NAGA NM_000262.3(NAGA): c.16G> A (p.Val6Met) single nucleotide variant Uncertain significance 22:42466286-42466286 22:42070282-42070282
10 NAGA NM_000262.3(NAGA): c.-306C> A single nucleotide variant Uncertain significance rs886057598 22:42466607-42466607 22:42070603-42070603
11 NAGA NM_000262.3(NAGA): c.-502A> C single nucleotide variant Uncertain significance rs886057600 22:42466803-42466803 22:42070799-42070799
12 NAGA NM_000262.3(NAGA): c.*1789del deletion Uncertain significance rs10713176 22:42454494-42454494 22:42058490-42058490
13 NAGA NM_000262.3(NAGA): c.*1090G> A single nucleotide variant Uncertain significance rs886057594 22:42455193-42455193 22:42059189-42059189
14 NAGA NM_000262.3(NAGA): c.*555C> T single nucleotide variant Uncertain significance rs141688392 22:42455728-42455728 22:42059724-42059724
15 NAGA NM_000262.3(NAGA): c.*176C> G single nucleotide variant Uncertain significance rs191051580 22:42456107-42456107 22:42060103-42060103
16 NAGA NM_000262.3(NAGA): c.549C> T (p.Ile183=) single nucleotide variant Uncertain significance rs374984089 22:42462762-42462762 22:42066758-42066758
17 NAGA NM_000262.3(NAGA): c.280G> A (p.Asp94Asn) single nucleotide variant Uncertain significance rs73167107 22:42463813-42463813 22:42067809-42067809
18 NAGA NM_000262.3(NAGA): c.19C> T (p.Leu7Phe) single nucleotide variant Uncertain significance rs886057597 22:42464576-42464576 22:42068572-42068572
19 NAGA NM_000262.3(NAGA): c.*1299C> T single nucleotide variant Uncertain significance rs886057592 22:42454984-42454984 22:42058980-42058980
20 NAGA NM_000262.3(NAGA): c.*1252T> C single nucleotide variant Uncertain significance rs886057593 22:42455031-42455031 22:42059027-42059027
21 NAGA NM_000262.3(NAGA): c.*926C> G single nucleotide variant Uncertain significance rs886057595 22:42455357-42455357 22:42059353-42059353
22 NAGA NM_000262.3(NAGA): c.*268G> A single nucleotide variant Uncertain significance rs886057596 22:42456015-42456015 22:42060011-42060011
23 NAGA NM_000262.3(NAGA): c.*155A> G single nucleotide variant Uncertain significance rs761125179 22:42456128-42456128 22:42060124-42060124
24 NAGA NM_000262.3(NAGA): c.638G> A (p.Arg213His) single nucleotide variant Uncertain significance rs781499383 22:42461863-42461863 22:42065859-42065859
25 NAGA NM_000262.3(NAGA): c.406G> A (p.Asp136Asn) single nucleotide variant Uncertain significance rs186173534 22:42463213-42463213 22:42067209-42067209
26 NAGA NM_000262.3(NAGA): c.110G> A (p.Arg37His) single nucleotide variant Uncertain significance rs199834981 22:42464485-42464485 22:42068481-42068481
27 NAGA NM_000262.3(NAGA): c.-43C> T single nucleotide variant Uncertain significance rs753592199 22:42466344-42466344 22:42070340-42070340
28 NAGA NM_000262.3(NAGA): c.*1696C> T single nucleotide variant Uncertain significance rs11703233 22:42454587-42454587 22:42058583-42058583
29 NAGA NM_000262.3(NAGA): c.*1501C> G single nucleotide variant Uncertain significance rs750373836 22:42454782-42454782 22:42058778-42058778
30 NAGA NM_000262.3(NAGA): c.1013T> C (p.Leu338Ser) single nucleotide variant Uncertain significance rs778343270 22:42457016-42457016 22:42061012-42061012
31 NAGA NM_000262.3(NAGA): c.993G> T (p.Leu331=) single nucleotide variant Uncertain significance rs147853281 22:42457036-42457036 22:42061032-42061032
32 NAGA NM_000262.3(NAGA): c.859C> T (p.Arg287Cys) single nucleotide variant Uncertain significance rs368220690 22:42458929-42458929 22:42062925-42062925
33 NAGA NM_000262.3(NAGA): c.25C> T (p.Leu9=) single nucleotide variant Uncertain significance rs147528904 22:42464570-42464570 22:42068566-42068566
34 NAGA NM_000262.3(NAGA): c.-496G> C single nucleotide variant Uncertain significance rs886057599 22:42466797-42466797 22:42070793-42070793
35 NAGA NM_000262.3(NAGA): c.*1035G> A single nucleotide variant Likely benign rs62238588 22:42455248-42455248 22:42059244-42059244
36 NAGA NM_000262.3(NAGA): c.*1814C> T single nucleotide variant Likely benign rs80313011 22:42454469-42454469 22:42058465-42058465
37 NAGA NM_000262.3(NAGA): c.*161T> C single nucleotide variant Likely benign rs150991002 22:42456122-42456122 22:42060118-42060118
38 NAGA NM_000262.3(NAGA): c.957+4C> G single nucleotide variant Likely benign rs55715427 22:42458827-42458827 22:42062823-42062823
39 NAGA NM_000262.3(NAGA): c.*143C> T single nucleotide variant Likely benign rs17002832 22:42456140-42456140 22:42060136-42060136
40 NAGA NM_000262.3(NAGA): c.*12A> C single nucleotide variant Likely benign rs2229547 22:42456271-42456271 22:42060267-42060267
41 NAGA NM_000262.3(NAGA): c.760-7C> A single nucleotide variant Likely benign rs150693978 22:42459035-42459035 22:42063031-42063031
42 NAGA NM_000262.3(NAGA): c.502+8A> T single nucleotide variant Likely benign rs375946807 22:42463109-42463109 22:42067105-42067105
43 NAGA NM_000262.3(NAGA): c.279G> A (p.Pro93=) single nucleotide variant Benign rs133369 22:42463814-42463814 22:42067810-42067810
44 NAGA NM_000262.3(NAGA): c.598-15C> T single nucleotide variant Benign rs2854827 22:42461918-42461918 22:42065914-42065914
45 NAGA NM_000262.3(NAGA): c.-208G> C single nucleotide variant Benign rs133375 22:42466509-42466509 22:42070505-42070505
46 NAGA NM_000262.3(NAGA): c.*1929C> T single nucleotide variant Benign rs5758566 22:42454354-42454354 22:42058350-42058350
47 NAGA NM_000262.3(NAGA): c.*1788_*1789del deletion Benign rs10713176 22:42454494-42454495 22:42058490-42058491
48 NAGA NM_000262.3(NAGA): c.*1333T> C single nucleotide variant Benign rs1063392 22:42454950-42454950 22:42058946-42058946

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

74
# 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
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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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