KANZD
MCID: KNZ001
MIFTS: 34

Kanzaki Disease (KANZD)

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

Aliases & Classifications for Kanzaki Disease

MalaCards integrated aliases for Kanzaki Disease:

Name: Kanzaki Disease 58 54 60 76 30 13 6 41
Alpha-N-Acetylgalactosaminidase Deficiency Type 2 54 60
Schindler Disease, Type Ii 58 74
Schindler Disease Type 2 54 60
Naga Deficiency Type 2 54 60
Alpha-N-Acetylgalactosaminidase Deficiency, Adult-Onset 58
Alpha-N-Acetylgalactosaminidase Deficiency Adult Onset 54
Adult-Onset Alpha-N-Acetylgalactosaminidase Deficiency 60
Alpha-N-Acetylgalactosaminidase Deficiency, Type Ii 58
Schindler Disease Type Ii 76
Naga Deficiency, Type Ii 58
Naga Deficiency Type Ii 76
Kanzd 76

Characteristics:

Orphanet epidemiological data:

60
alpha-n-acetylgalactosaminidase deficiency type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
adult onset
allelic disorder to schindler disease


HPO:

33
kanzaki disease:
Onset and clinical course adult onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Kanzaki Disease

NIH Rare Diseases : 54 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 dry skin and vertigo. An important gene associated with Kanzaki Disease is NAGA (Alpha-N-Acetylgalactosaminidase). Affiliated tissues include endothelial, smooth muscle and skin, and related phenotypes are intellectual disability, mild and subcutaneous nodule

OMIM : 58 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 : 76 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 31.7 LOC107985551 NAGA WBP2NL
2 schindler disease, type i 11.1
3 angiokeratoma 10.1

Symptoms & Phenotypes for Kanzaki Disease

Human phenotypes related to Kanzaki Disease:

60 33 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability, mild 60 33 hallmark (90%) Very frequent (99-80%) HP:0001256
2 subcutaneous nodule 60 33 hallmark (90%) Very frequent (99-80%) HP:0001482
3 hyperkeratosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000962
4 vertigo 60 33 hallmark (90%) Very frequent (99-80%) HP:0002321
5 telangiectasia of the skin 60 33 hallmark (90%) Very frequent (99-80%) HP:0100585
6 papule 60 33 hallmark (90%) Very frequent (99-80%) HP:0200034
7 lip telangiectasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000214
8 angiokeratoma corporis diffusum 60 33 hallmark (90%) Very frequent (99-80%) HP:0001071
9 telangiectasia of the oral mucosa 60 33 hallmark (90%) Very frequent (99-80%) HP:0007428
10 coarse facial features 60 33 frequent (33%) Frequent (79-30%) HP:0000280
11 hearing impairment 60 33 frequent (33%) Frequent (79-30%) HP:0000365
12 depressed nasal bridge 60 33 frequent (33%) Frequent (79-30%) HP:0005280
13 thick vermilion border 60 33 frequent (33%) Frequent (79-30%) HP:0012471
14 cardiomegaly 60 33 frequent (33%) Frequent (79-30%) HP:0001640
15 peripheral neuropathy 60 33 frequent (33%) Frequent (79-30%) HP:0009830
16 opacification of the corneal stroma 60 33 frequent (33%) Frequent (79-30%) HP:0007759
17 lymphedema 60 33 frequent (33%) Frequent (79-30%) HP:0001004
18 tinnitus 60 33 frequent (33%) Frequent (79-30%) HP:0000360
19 sensorineural hearing impairment 33 HP:0000407
20 cognitive impairment 33 HP:0100543
21 aminoaciduria 33 HP:0003355
22 abnormality of the eye 33 HP:0000478
23 thick lower lip vermilion 33 HP:0000179
24 increased urinary o-linked sialopeptides 33 HP:0003461
25 dry skin 33 HP:0000958
26 peripheral axonal neuropathy 33 HP:0003477
27 distal muscle weakness 33 HP:0002460
28 cerebral atrophy 33 HP:0002059
29 distal sensory impairment 33 HP:0002936
30 distal sensory impairment of all modalities 33 HP:0003409
31 axonal degeneration 33 HP:0040078
32 white mater abnormalities in the posterior periventricular region 33 HP:0006812

Symptoms via clinical synopsis from OMIM:

58
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 sensory impairment of all modalities
distal limb muscle weakness
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

UMLS symptoms related to Kanzaki Disease:


dry skin, vertigo

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 30 NAGA

Anatomical Context for Kanzaki Disease

MalaCards organs/tissues related to Kanzaki Disease:

42
Endothelial, Smooth Muscle, Skin, Eye, Adipocyte

Publications for Kanzaki Disease

Articles related to Kanzaki Disease:

(show all 13)
# Title Authors Year
1
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
2
Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease). ( 14685826 )
2004
3
Neurologic manifestations of Kanzaki disease. ( 15136691 )
2004
4
A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Ménière's syndrome and without mental retardation. ( 11251574 )
2001
5
[Schindler disease/Kanzaki disease [alpha-N-acetylgalactosaminidase deficiency]]. ( 9645085 )
1998
6
Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype. ( 8782044 )
1996
7
Histopathologic and ultrastructural studies of angiokeratoma corporis diffusum in Kanzaki disease. ( 7897017 )
1995
8
[Schindler disease/Kanzaki disease]. ( 8577046 )
1995
9
The molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes angiokeratoma corporis diffusum with glycopeptiduria. ( 8040340 )
1994
10
Mild phenotypic expression of alpha-N-acetylgalactosaminidase deficiency in two adult siblings. ( 7707696 )
1994
11
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
12
Molecular cloning of two species of cDNAs for human alpha-N-acetylgalactosaminidase and expression in mammalian cells. ( 2372288 )
1990
13
Novel lysosomal glycoaminoacid storage disease with angiokeratoma corporis diffusum. ( 2564952 )
1989

Variations for Kanzaki Disease

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

76
# 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 84)
# Gene Variation Type Significance SNP ID Assembly Location
1 NAGA NM_000262.2(NAGA): c.973G> A (p.Glu325Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121434529 GRCh37 Chromosome 22, 42457056: 42457056
2 NAGA NM_000262.2(NAGA): c.973G> A (p.Glu325Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121434529 GRCh38 Chromosome 22, 42061052: 42061052
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.577G> T (p.Glu193Ter) single nucleotide variant Pathogenic rs121434531 GRCh37 Chromosome 22, 42462734: 42462734
6 NAGA NM_000262.2(NAGA): c.577G> T (p.Glu193Ter) single nucleotide variant Pathogenic rs121434531 GRCh38 Chromosome 22, 42066730: 42066730
7 NAGA NM_000262.2(NAGA): c.986G> A (p.Arg329Gln) single nucleotide variant Pathogenic rs121434533 GRCh37 Chromosome 22, 42457043: 42457043
8 NAGA NM_000262.2(NAGA): c.986G> A (p.Arg329Gln) single nucleotide variant Pathogenic rs121434533 GRCh38 Chromosome 22, 42061039: 42061039
9 NAGA NM_000262.2(NAGA): c.279G> A (p.Pro93=) single nucleotide variant Benign rs133369 GRCh37 Chromosome 22, 42463814: 42463814
10 NAGA NM_000262.2(NAGA): c.279G> A (p.Pro93=) single nucleotide variant Benign rs133369 GRCh38 Chromosome 22, 42067810: 42067810
11 NAGA NM_000262.2(NAGA): c.598-15C> T single nucleotide variant Benign rs2854827 GRCh37 Chromosome 22, 42461918: 42461918
12 NAGA NM_000262.2(NAGA): c.598-15C> T single nucleotide variant Benign rs2854827 GRCh38 Chromosome 22, 42065914: 42065914
13 NAGA NM_000262.2(NAGA): c.*1789delT deletion Uncertain significance rs10713176 GRCh38 Chromosome 22, 42058490: 42058490
14 NAGA NM_000262.2(NAGA): c.*1789delT deletion Uncertain significance rs10713176 GRCh37 Chromosome 22, 42454494: 42454494
15 NAGA NM_000262.2(NAGA): c.*12A> C single nucleotide variant Likely benign rs2229547 GRCh37 Chromosome 22, 42456271: 42456271
16 NAGA NM_000262.2(NAGA): c.*12A> C single nucleotide variant Likely benign rs2229547 GRCh38 Chromosome 22, 42060267: 42060267
17 NAGA NM_000262.2(NAGA): c.760-7C> A single nucleotide variant Likely benign rs150693978 GRCh37 Chromosome 22, 42459035: 42459035
18 NAGA NM_000262.2(NAGA): c.760-7C> A single nucleotide variant Likely benign rs150693978 GRCh38 Chromosome 22, 42063031: 42063031
19 NAGA NM_000262.2(NAGA): c.-502A> C single nucleotide variant Uncertain significance rs886057600 GRCh38 Chromosome 22, 42070799: 42070799
20 NAGA NM_000262.2(NAGA): c.-502A> C single nucleotide variant Uncertain significance rs886057600 GRCh37 Chromosome 22, 42466803: 42466803
21 NAGA NM_000262.2(NAGA): c.*1299C> T single nucleotide variant Uncertain significance rs886057592 GRCh37 Chromosome 22, 42454984: 42454984
22 NAGA NM_000262.2(NAGA): c.*1299C> T single nucleotide variant Uncertain significance rs886057592 GRCh38 Chromosome 22, 42058980: 42058980
23 NAGA NM_000262.2(NAGA): c.*1252T> C single nucleotide variant Uncertain significance rs886057593 GRCh37 Chromosome 22, 42455031: 42455031
24 NAGA NM_000262.2(NAGA): c.*1252T> C single nucleotide variant Uncertain significance rs886057593 GRCh38 Chromosome 22, 42059027: 42059027
25 NAGA NM_000262.2(NAGA): c.*926C> G single nucleotide variant Uncertain significance rs886057595 GRCh37 Chromosome 22, 42455357: 42455357
26 NAGA NM_000262.2(NAGA): c.*926C> G single nucleotide variant Uncertain significance rs886057595 GRCh38 Chromosome 22, 42059353: 42059353
27 NAGA NM_000262.2(NAGA): c.*268G> A single nucleotide variant Uncertain significance rs886057596 GRCh37 Chromosome 22, 42456015: 42456015
28 NAGA NM_000262.2(NAGA): c.*268G> A single nucleotide variant Uncertain significance rs886057596 GRCh38 Chromosome 22, 42060011: 42060011
29 NAGA NM_000262.2(NAGA): c.*161T> C single nucleotide variant Likely benign rs150991002 GRCh37 Chromosome 22, 42456122: 42456122
30 NAGA NM_000262.2(NAGA): c.*161T> C single nucleotide variant Likely benign rs150991002 GRCh38 Chromosome 22, 42060118: 42060118
31 NAGA NM_000262.2(NAGA): c.*155A> G single nucleotide variant Uncertain significance rs761125179 GRCh37 Chromosome 22, 42456128: 42456128
32 NAGA NM_000262.2(NAGA): c.*155A> G single nucleotide variant Uncertain significance rs761125179 GRCh38 Chromosome 22, 42060124: 42060124
33 NAGA NM_000262.2(NAGA): c.638G> A (p.Arg213His) single nucleotide variant Uncertain significance rs781499383 GRCh37 Chromosome 22, 42461863: 42461863
34 NAGA NM_000262.2(NAGA): c.638G> A (p.Arg213His) single nucleotide variant Uncertain significance rs781499383 GRCh38 Chromosome 22, 42065859: 42065859
35 NAGA NM_000262.2(NAGA): c.406G> A (p.Asp136Asn) single nucleotide variant Uncertain significance rs186173534 GRCh37 Chromosome 22, 42463213: 42463213
36 NAGA NM_000262.2(NAGA): c.406G> A (p.Asp136Asn) single nucleotide variant Uncertain significance rs186173534 GRCh38 Chromosome 22, 42067209: 42067209
37 NAGA NM_000262.2(NAGA): c.110G> A (p.Arg37His) single nucleotide variant Uncertain significance rs199834981 GRCh38 Chromosome 22, 42068481: 42068481
38 NAGA NM_000262.2(NAGA): c.110G> A (p.Arg37His) single nucleotide variant Uncertain significance rs199834981 GRCh37 Chromosome 22, 42464485: 42464485
39 NAGA NM_000262.2(NAGA): c.-43C> T single nucleotide variant Uncertain significance rs753592199 GRCh38 Chromosome 22, 42070340: 42070340
40 NAGA NM_000262.2(NAGA): c.-43C> T single nucleotide variant Uncertain significance rs753592199 GRCh37 Chromosome 22, 42466344: 42466344
41 NAGA NM_000262.2(NAGA): c.*1929C> T single nucleotide variant Benign rs5758566 GRCh38 Chromosome 22, 42058350: 42058350
42 NAGA NM_000262.2(NAGA): c.*1929C> T single nucleotide variant Benign rs5758566 GRCh37 Chromosome 22, 42454354: 42454354
43 NAGA NM_000262.2(NAGA): c.*1814C> T single nucleotide variant Likely benign rs80313011 GRCh38 Chromosome 22, 42058465: 42058465
44 NAGA NM_000262.2(NAGA): c.*1814C> T single nucleotide variant Likely benign rs80313011 GRCh37 Chromosome 22, 42454469: 42454469
45 NAGA NM_000262.2(NAGA): c.*1788_*1789delTT deletion Benign rs10713176 GRCh38 Chromosome 22, 42058490: 42058491
46 NAGA NM_000262.2(NAGA): c.*1788_*1789delTT deletion Benign rs10713176 GRCh37 Chromosome 22, 42454494: 42454495
47 NAGA NM_000262.2(NAGA): c.*1696C> T single nucleotide variant Uncertain significance rs11703233 GRCh38 Chromosome 22, 42058583: 42058583
48 NAGA NM_000262.2(NAGA): c.*1696C> T single nucleotide variant Uncertain significance rs11703233 GRCh37 Chromosome 22, 42454587: 42454587
49 NAGA NM_000262.2(NAGA): c.*1501C> G single nucleotide variant Uncertain significance rs750373836 GRCh37 Chromosome 22, 42454782: 42454782
50 NAGA NM_000262.2(NAGA): c.*1501C> G single nucleotide variant Uncertain significance rs750373836 GRCh38 Chromosome 22, 42058778: 42058778

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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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