MCID: KNZ001
MIFTS: 35

Kanzaki Disease

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

Aliases & Classifications for Kanzaki Disease

MalaCards integrated aliases for Kanzaki Disease:

Name: Kanzaki Disease 57 53 59 75 29 13 6 40
Alpha-N-Acetylgalactosaminidase Deficiency Type 2 53 59
Schindler Disease, Type Ii 57 73
Schindler Disease Type 2 53 59
Naga Deficiency Type 2 53 59
Alpha-N-Acetylgalactosaminidase Deficiency, Adult-Onset 57
Alpha-N-Acetylgalactosaminidase Deficiency Adult Onset 53
Adult-Onset Alpha-N-Acetylgalactosaminidase Deficiency 59
Alpha-N-Acetylgalactosaminidase Deficiency, Type Ii 57
Schindler Disease Type Ii 75
Naga Deficiency, Type Ii 57
Naga Deficiency Type Ii 75
Kanzd 75

Characteristics:

Orphanet epidemiological data:

59
alpha-n-acetylgalactosaminidase deficiency type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
adult onset
allelic disorder to schindler disease


HPO:

32
kanzaki disease:
Onset and clinical course adult onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Kanzaki Disease

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79280Disease definitionAlpha-N-acetylgalactosaminidase (NAGA) deficiency type 2 is a very rare mild adult type of NAGA deficiency (see this term) with the features of angiokeratoma corporis diffusum (see this term) and mild sensory neuropathy.EpidemiologyPrevalence of this disorder is not known but less than 20 cases have been reported to date for NAGA deficiency.Clinical descriptionThis disorder is clinically heterogeneous. Some patients have been reported to have, in addition to angiokeratoma, mild intellectual impairment, but no neurologic signs. Another patient had lymphedema, cardiomegaly, corneal opacity and slight facial coarsening including thick lips, a depressed nasal bridge and an enlarged tip of the nose. Other facultative features consist of tinnitus, hearing loss and vertigo (Meniere disease) (see this term). Pathological characteristics are comprised of vacuolization seen in the blood and dermal cells including the endothelial cells of blood and lymphatic vessels, pericytes, fibrocytes, fat cells, Schwann cells, axons, arrector pili smooth muscle cells, and eccrine sweat gland cells. Vacuolization is most prominent in vascular endothelial cells and the secretory portion of sweat glands.EtiologyDifferent causal homozygousmutations of the NAGA gene (22q13.2) have been described in the reported patients. These mutations lead to the dysfunction, instability and rapid degradation of the lysosomal protein, NAGA. Lack of this enzyme activity leads to impaired catabolism and accumulation of undegraded glycoconjugates in the tertiary lysosomes.Genetic counselingTransmission is autosomal recessive and genetic counseling is possible.Visit the Orphanet disease page for more resources.

MalaCards based summary : Kanzaki Disease, also known as alpha-n-acetylgalactosaminidase deficiency type 2, is related to schindler disease and schindler disease, type i, and has symptoms including vertigo and dry skin. An important gene associated with Kanzaki Disease is NAGA (Alpha-N-Acetylgalactosaminidase). Affiliated tissues include endothelial, smooth muscle and skin, and related phenotypes are coarse facial features and hearing impairment

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

UniProtKB/Swiss-Prot : 75 Kanzaki disease: Autosomal recessive disorder characterized by late-onset, angiokeratoma corporis diffusum and mild intellectual impairment.

Related Diseases for Kanzaki Disease

Diseases related to Kanzaki Disease via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 schindler disease 30.4 LOC107985551 NAGA WBP2NL
2 schindler disease, type i 10.9
3 angiokeratoma 9.9
4 iga glomerulonephritis 9.3 ACE NAGA

Symptoms & Phenotypes for Kanzaki Disease

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Nose:
depressed nasal bridge
enlarged nasal tip

Laboratory Abnormalities:
increased urinary o-linked sialopeptides
decreased or absent alpha-n-acetylgalactosaminidase protein
decreased or absent alpha-n-acetylgalactosaminidase activity
diverse tissue cell types (vascular endothelial cells, adipocytes, schwann cells, leukocytes) have membrane-lined cytoplasmic vacuoles with amorphous and filamentous material
glycoamino aciduria

Neurologic Central Nervous System:
vertigo
intellectual impairment, mild
atrophy of the cerebrum seen on mri (in some patients)
white matter abnormalities in the posterior periventricular region

Head And Neck Mouth:
thick lips

Head And Neck Ears:
sensorineural hearing loss
meniere syndrome

Skin Nails Hair Skin:
hyperkeratosis
dry skin
angiokeratoma corporis diffusum
maculopapular eruption, diffuse
telangiectasia on lips and oral mucosa

Muscle Soft Tissue:
lymphedema

Neurologic Peripheral Nervous System:
peripheral axonal neuropathy
distal limb muscle weakness
distal sensory impairment of all modalities
decreased density of myelinated fibers and axonal degeneration seen on sural nerve biopsy

Head And Neck Face:
coarse facies

Head And Neck Eyes:
conjunctiva shows dilated blood vessels
fundi show dilated blood vessels with corkscrew-like tortuosity


Clinical features from OMIM:

609242

Human phenotypes related to Kanzaki Disease:

59 32 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 coarse facial features 59 32 frequent (33%) Frequent (79-30%) HP:0000280
2 hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000365
3 depressed nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0005280
4 thick vermilion border 59 32 frequent (33%) Frequent (79-30%) HP:0012471
5 intellectual disability, mild 59 32 hallmark (90%) Very frequent (99-80%) HP:0001256
6 subcutaneous nodule 59 32 hallmark (90%) Very frequent (99-80%) HP:0001482
7 cardiomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0001640
8 hyperkeratosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000962
9 peripheral neuropathy 59 32 frequent (33%) Frequent (79-30%) HP:0009830
10 opacification of the corneal stroma 59 32 frequent (33%) Frequent (79-30%) HP:0007759
11 lymphedema 59 32 frequent (33%) Frequent (79-30%) HP:0001004
12 vertigo 59 32 hallmark (90%) Very frequent (99-80%) HP:0002321
13 telangiectasia of the skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0100585
14 tinnitus 59 32 frequent (33%) Frequent (79-30%) HP:0000360
15 papule 59 32 hallmark (90%) Very frequent (99-80%) HP:0200034
16 lip telangiectasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000214
17 angiokeratoma corporis diffusum 59 32 hallmark (90%) Very frequent (99-80%) HP:0001071
18 telangiectasia of the oral mucosa 59 32 hallmark (90%) Very frequent (99-80%) HP:0007428
19 sensorineural hearing impairment 32 HP:0000407
20 cognitive impairment 32 HP:0100543
21 aminoaciduria 32 HP:0003355
22 abnormality of the eye 32 HP:0000478
23 thick lower lip vermilion 32 HP:0000179
24 increased urinary o-linked sialopeptides 32 HP:0003461
25 dry skin 32 HP:0000958
26 distal muscle weakness 32 HP:0002460
27 cerebral atrophy 32 HP:0002059
28 distal sensory impairment 32 HP:0002936
29 peripheral axonal neuropathy 32 HP:0003477
30 axonal degeneration 32 HP:0040078
31 distal sensory impairment of all modalities 32 HP:0003409
32 white mater abnormalities in the posterior periventricular region 32 HP:0006812

UMLS symptoms related to Kanzaki Disease:


vertigo, dry skin

Drugs & Therapeutics for Kanzaki Disease

Search Clinical Trials , NIH Clinical Center for Kanzaki Disease

Genetic Tests for Kanzaki Disease

Genetic tests related to Kanzaki Disease:

# Genetic test Affiliating Genes
1 Kanzaki Disease 29 NAGA

Anatomical Context for Kanzaki Disease

MalaCards organs/tissues related to Kanzaki Disease:

41
Endothelial, Smooth Muscle, Skin, Eye, Adipocyte

Publications for Kanzaki Disease

Articles related to Kanzaki Disease:

# Title Authors Year
1
The 1.9 A structure of human alpha-N-acetylgalactosaminidase: the molecular basis of Schindler and Kanzaki diseases. ( 19683538 )
2009
2
Three dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes. ( 15619430 )
2005
3
Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease). ( 14685826 )
2004
4
Neurologic manifestations of Kanzaki disease. ( 15136691 )
2004
5
[Schindler disease/Kanzaki disease [alpha-N-acetylgalactosaminidase deficiency]]. ( 9645085 )
1998
6
Histopathologic and ultrastructural studies of angiokeratoma corporis diffusum in Kanzaki disease. ( 7897017 )
1995
7
[Schindler disease/Kanzaki disease]. ( 8577046 )
1995
8
Isolation and characterization of major urinary amino acid O-glycosides and a dipeptide O-glycoside from a new lysosomal storage disorder (Kanzaki disease). Excessive excretion of serine- and threonine-linked glycan in the patient urine. ( 2104850 )
1990

Variations for Kanzaki Disease

UniProtKB/Swiss-Prot genetic disease variations for Kanzaki Disease:

75
# Symbol AA change Variation ID SNP ID
1 NAGA p.Arg329Trp VAR_000498 rs121434530
2 NAGA p.Arg329Gln VAR_022525 rs121434533

ClinVar genetic disease variations for Kanzaki Disease:

6
(show top 50) (show all 82)
# Gene Variation Type Significance SNP ID Assembly Location
1 NAGA NM_000262.2(NAGA): c.577G> T (p.Glu193Ter) single nucleotide variant Pathogenic rs121434531 GRCh37 Chromosome 22, 42462734: 42462734
2 NAGA NM_000262.2(NAGA): c.577G> T (p.Glu193Ter) single nucleotide variant Pathogenic rs121434531 GRCh38 Chromosome 22, 42066730: 42066730
3 NAGA NM_000262.2(NAGA): c.985C> T (p.Arg329Trp) single nucleotide variant Pathogenic rs121434530 GRCh37 Chromosome 22, 42457044: 42457044
4 NAGA NM_000262.2(NAGA): c.985C> T (p.Arg329Trp) single nucleotide variant Pathogenic rs121434530 GRCh38 Chromosome 22, 42061040: 42061040
5 NAGA NM_000262.2(NAGA): c.986G> A (p.Arg329Gln) single nucleotide variant Pathogenic rs121434533 GRCh37 Chromosome 22, 42457043: 42457043
6 NAGA NM_000262.2(NAGA): c.986G> A (p.Arg329Gln) single nucleotide variant Pathogenic rs121434533 GRCh38 Chromosome 22, 42061039: 42061039
7 NAGA NM_000262.2(NAGA): c.279G> A (p.Pro93=) single nucleotide variant Benign rs133369 GRCh37 Chromosome 22, 42463814: 42463814
8 NAGA NM_000262.2(NAGA): c.279G> A (p.Pro93=) single nucleotide variant Benign rs133369 GRCh38 Chromosome 22, 42067810: 42067810
9 NAGA NM_000262.2(NAGA): c.598-15C> T single nucleotide variant Benign rs2854827 GRCh37 Chromosome 22, 42461918: 42461918
10 NAGA NM_000262.2(NAGA): c.598-15C> T single nucleotide variant Benign rs2854827 GRCh38 Chromosome 22, 42065914: 42065914
11 NAGA NM_000262.2(NAGA): c.*1789delT deletion Uncertain significance rs10713176 GRCh38 Chromosome 22, 42058490: 42058490
12 NAGA NM_000262.2(NAGA): c.*1789delT deletion Uncertain significance rs10713176 GRCh37 Chromosome 22, 42454494: 42454494
13 NAGA NM_000262.2(NAGA): c.*12A> C single nucleotide variant Likely benign rs2229547 GRCh37 Chromosome 22, 42456271: 42456271
14 NAGA NM_000262.2(NAGA): c.*12A> C single nucleotide variant Likely benign rs2229547 GRCh38 Chromosome 22, 42060267: 42060267
15 NAGA NM_000262.2(NAGA): c.760-7C> A single nucleotide variant Likely benign rs150693978 GRCh37 Chromosome 22, 42459035: 42459035
16 NAGA NM_000262.2(NAGA): c.760-7C> A single nucleotide variant Likely benign rs150693978 GRCh38 Chromosome 22, 42063031: 42063031
17 NAGA NM_000262.2(NAGA): c.-502A> C single nucleotide variant Uncertain significance rs886057600 GRCh38 Chromosome 22, 42070799: 42070799
18 NAGA NM_000262.2(NAGA): c.-502A> C single nucleotide variant Uncertain significance rs886057600 GRCh37 Chromosome 22, 42466803: 42466803
19 NAGA NM_000262.2(NAGA): c.*1299C> T single nucleotide variant Uncertain significance rs886057592 GRCh37 Chromosome 22, 42454984: 42454984
20 NAGA NM_000262.2(NAGA): c.*1299C> T single nucleotide variant Uncertain significance rs886057592 GRCh38 Chromosome 22, 42058980: 42058980
21 NAGA NM_000262.2(NAGA): c.*1252T> C single nucleotide variant Uncertain significance rs886057593 GRCh37 Chromosome 22, 42455031: 42455031
22 NAGA NM_000262.2(NAGA): c.*1252T> C single nucleotide variant Uncertain significance rs886057593 GRCh38 Chromosome 22, 42059027: 42059027
23 NAGA NM_000262.2(NAGA): c.*926C> G single nucleotide variant Uncertain significance rs886057595 GRCh37 Chromosome 22, 42455357: 42455357
24 NAGA NM_000262.2(NAGA): c.*926C> G single nucleotide variant Uncertain significance rs886057595 GRCh38 Chromosome 22, 42059353: 42059353
25 NAGA NM_000262.2(NAGA): c.*268G> A single nucleotide variant Uncertain significance rs886057596 GRCh37 Chromosome 22, 42456015: 42456015
26 NAGA NM_000262.2(NAGA): c.*268G> A single nucleotide variant Uncertain significance rs886057596 GRCh38 Chromosome 22, 42060011: 42060011
27 NAGA NM_000262.2(NAGA): c.*161T> C single nucleotide variant Likely benign rs150991002 GRCh37 Chromosome 22, 42456122: 42456122
28 NAGA NM_000262.2(NAGA): c.*161T> C single nucleotide variant Likely benign rs150991002 GRCh38 Chromosome 22, 42060118: 42060118
29 NAGA NM_000262.2(NAGA): c.*155A> G single nucleotide variant Uncertain significance rs761125179 GRCh37 Chromosome 22, 42456128: 42456128
30 NAGA NM_000262.2(NAGA): c.*155A> G single nucleotide variant Uncertain significance rs761125179 GRCh38 Chromosome 22, 42060124: 42060124
31 NAGA NM_000262.2(NAGA): c.638G> A (p.Arg213His) single nucleotide variant Uncertain significance rs781499383 GRCh37 Chromosome 22, 42461863: 42461863
32 NAGA NM_000262.2(NAGA): c.638G> A (p.Arg213His) single nucleotide variant Uncertain significance rs781499383 GRCh38 Chromosome 22, 42065859: 42065859
33 NAGA NM_000262.2(NAGA): c.406G> A (p.Asp136Asn) single nucleotide variant Uncertain significance rs186173534 GRCh37 Chromosome 22, 42463213: 42463213
34 NAGA NM_000262.2(NAGA): c.406G> A (p.Asp136Asn) single nucleotide variant Uncertain significance rs186173534 GRCh38 Chromosome 22, 42067209: 42067209
35 NAGA NM_000262.2(NAGA): c.110G> A (p.Arg37His) single nucleotide variant Uncertain significance rs199834981 GRCh38 Chromosome 22, 42068481: 42068481
36 NAGA NM_000262.2(NAGA): c.110G> A (p.Arg37His) single nucleotide variant Uncertain significance rs199834981 GRCh37 Chromosome 22, 42464485: 42464485
37 NAGA NM_000262.2(NAGA): c.-43C> T single nucleotide variant Uncertain significance rs753592199 GRCh38 Chromosome 22, 42070340: 42070340
38 NAGA NM_000262.2(NAGA): c.-43C> T single nucleotide variant Uncertain significance rs753592199 GRCh37 Chromosome 22, 42466344: 42466344
39 NAGA NM_000262.2(NAGA): c.*1929C> T single nucleotide variant Benign rs5758566 GRCh38 Chromosome 22, 42058350: 42058350
40 NAGA NM_000262.2(NAGA): c.*1929C> T single nucleotide variant Benign rs5758566 GRCh37 Chromosome 22, 42454354: 42454354
41 NAGA NM_000262.2(NAGA): c.*1814C> T single nucleotide variant Likely benign rs80313011 GRCh38 Chromosome 22, 42058465: 42058465
42 NAGA NM_000262.2(NAGA): c.*1814C> T single nucleotide variant Likely benign rs80313011 GRCh37 Chromosome 22, 42454469: 42454469
43 NAGA NM_000262.2(NAGA): c.*1788_*1789delTT deletion Benign rs539279819 GRCh38 Chromosome 22, 42058490: 42058491
44 NAGA NM_000262.2(NAGA): c.*1788_*1789delTT deletion Benign rs539279819 GRCh37 Chromosome 22, 42454494: 42454495
45 NAGA NM_000262.2(NAGA): c.*1696C> T single nucleotide variant Uncertain significance rs11703233 GRCh38 Chromosome 22, 42058583: 42058583
46 NAGA NM_000262.2(NAGA): c.*1696C> T single nucleotide variant Uncertain significance rs11703233 GRCh37 Chromosome 22, 42454587: 42454587
47 NAGA NM_000262.2(NAGA): c.*1501C> G single nucleotide variant Uncertain significance rs750373836 GRCh37 Chromosome 22, 42454782: 42454782
48 NAGA NM_000262.2(NAGA): c.*1501C> G single nucleotide variant Uncertain significance rs750373836 GRCh38 Chromosome 22, 42058778: 42058778
49 NAGA NM_000262.2(NAGA): c.*1333T> C single nucleotide variant Benign rs1063392 GRCh37 Chromosome 22, 42454950: 42454950
50 NAGA NM_000262.2(NAGA): c.*1333T> C single nucleotide variant Benign rs1063392 GRCh38 Chromosome 22, 42058946: 42058946

Expression for Kanzaki Disease

Search GEO for disease gene expression data for Kanzaki Disease.

Pathways for Kanzaki Disease

GO Terms for Kanzaki Disease

Cellular components related to Kanzaki Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 8.62 ACE NAGA

Sources for Kanzaki Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....