MCID: KNZ001
MIFTS: 36

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 53 49 55 71 28 13
Alpha-N-Acetylgalactosaminidase Deficiency Type 2 49 55
Schindler Disease, Type Ii 53 69
Schindler Disease Type 2 49 55
Naga Deficiency Type 2 49 55
Alpha-N-Acetylgalactosaminidase Deficiency, Adult-Onset 53
Alpha-N-Acetylgalactosaminidase Deficiency Adult Onset 49
Adult-Onset Alpha-N-Acetylgalactosaminidase Deficiency 55
Alpha-N-Acetylgalactosaminidase Deficiency, Type Ii 53
Schindler Disease Type Ii 71
Naga Deficiency, Type Ii 53
Naga Deficiency Type Ii 71
Kanzd 71

Characteristics:

Orphanet epidemiological data:

55
alpha-n-acetylgalactosaminidase deficiency type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
adult onset
allelic disorder to schindler disease


HPO:

31
kanzaki disease:
Onset and clinical course adult onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Kanzaki Disease

NIH Rare Diseases : 49 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. Last updated: 6/1/2013

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, coarse facial features and hearing impairment. An important gene associated with Kanzaki Disease is NAGA (Alpha-N-Acetylgalactosaminidase). Affiliated tissues include endothelial, smooth muscle and skin.

OMIM : 53 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 : 71 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 11.4
2 schindler disease, type i 10.9
3 angiokeratoma 9.9
4 iga glomerulonephritis 9.4 ACE NAGA

Symptoms & Phenotypes for Kanzaki Disease

Symptoms via clinical synopsis from OMIM:

53
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 Nose:
depressed nasal bridge
enlarged nasal tip

Muscle Soft Tissue:
lymphedema

Head And Neck Mouth:
thick lips

Head And Neck Ears:
sensorineural hearing loss
meniere syndrome

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

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 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:

55 31 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 vertigo 55 31 hallmark (90%) Very frequent (99-80%) HP:0002321
2 coarse facial features 55 31 frequent (33%) Frequent (79-30%) HP:0000280
3 hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000365
4 depressed nasal bridge 55 31 frequent (33%) Frequent (79-30%) HP:0005280
5 thick vermilion border 55 31 frequent (33%) Frequent (79-30%) HP:0012471
6 intellectual disability, mild 55 31 hallmark (90%) Very frequent (99-80%) HP:0001256
7 subcutaneous nodule 55 31 hallmark (90%) Very frequent (99-80%) HP:0001482
8 cardiomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0001640
9 hyperkeratosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000962
10 peripheral neuropathy 55 31 frequent (33%) Frequent (79-30%) HP:0009830
11 opacification of the corneal stroma 55 31 frequent (33%) Frequent (79-30%) HP:0007759
12 lymphedema 55 31 frequent (33%) Frequent (79-30%) HP:0001004
13 telangiectasia of the skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0100585
14 tinnitus 55 31 frequent (33%) Frequent (79-30%) HP:0000360
15 papule 55 31 hallmark (90%) Very frequent (99-80%) HP:0200034
16 lip telangiectasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000214
17 angiokeratoma corporis diffusum 55 31 hallmark (90%) Very frequent (99-80%) HP:0001071
18 telangiectasia of the oral mucosa 55 31 hallmark (90%) Very frequent (99-80%) HP:0007428
19 dry skin 31 HP:0000958
20 sensorineural hearing impairment 31 HP:0000407
21 cognitive impairment 31 HP:0100543
22 aminoaciduria 31 HP:0003355
23 abnormality of the eye 31 HP:0000478
24 thick lower lip vermilion 31 HP:0000179
25 increased urinary o-linked sialopeptides 31 HP:0003461
26 distal muscle weakness 31 HP:0002460
27 cerebral atrophy 31 HP:0002059
28 distal sensory impairment 31 HP:0002936
29 peripheral axonal neuropathy 31 HP:0003477
30 axonal degeneration 31 HP:0040078
31 distal sensory impairment of all modalities 31 HP:0003409
32 white mater abnormalities in the posterior periventricular region 31 HP:0006812

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 28 NAGA

Anatomical Context for Kanzaki Disease

MalaCards organs/tissues related to Kanzaki Disease:

38
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
[Schindler disease/Kanzaki disease]. ( 8577046 )
1995
7
Histopathologic and ultrastructural studies of angiokeratoma corporis diffusum in Kanzaki disease. ( 7897017 )
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:

71
# 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
# Gene Variation Type Significance SNP ID Assembly Location
1 NAGA NM_000262.2(NAGA): c.985C> T (p.Arg329Trp) single nucleotide variant Pathogenic rs121434530 GRCh37 Chromosome 22, 42457044: 42457044
2 NAGA NM_000262.2(NAGA): c.577G> T (p.Glu193Ter) single nucleotide variant Pathogenic rs121434531 GRCh37 Chromosome 22, 42462734: 42462734
3 NAGA NM_000262.2(NAGA): c.986G> A (p.Arg329Gln) single nucleotide variant Pathogenic rs121434533 GRCh37 Chromosome 22, 42457043: 42457043

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

Molecular functions related to Kanzaki Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 8.62 ACE NAGA

Sources for Kanzaki Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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