Alpha-N-acetylgalactosaminidase deficiency type 2

General Information (adopted from Orphanet):

Synonyms, Signs: ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY, TYPE II
ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY, ADULT-ONSET
NAGA DEFICIENCY, TYPE II
SCHINDLER DISEASE, TYPE II
Schindler disease type 2
Adult-onset Alpha-N-acetylgalactosaminidase deficiency
NAGA deficiency type 2
Kanzaki disease
Number of Symptoms 49
OrphanetNr: 79280
OMIM Id: 609242
ICD-10: E77.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Adult
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Alpha-N-acetylgalactosaminidase deficiency
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000481) Abnormality of the cornea Frequent [Orphanet] 124 / 7739
2
 (HPO:0003461) Increased urinary O-linked sialopeptides 5 / 7739
3
 (HPO:0003355) Aminoaciduria 65 / 7739
4
 (HPO:0001640) Cardiomegaly Frequent [Orphanet] 81 / 7739
5
 (HPO:0001004) Lymphedema Frequent [Orphanet] 62 / 7739
6
 (HPO:0002460) Distal muscle weakness 122 / 7739
7
 (HPO:0003477) Peripheral axonal neuropathy 62 / 7739
8
 (HPO:0003409) Distal sensory impairment of all modalities 3 / 7739
9
 (HPO:0002936) Distal sensory impairment 96 / 7739
10
 (HPO:0009830) Peripheral neuropathy Frequent [Orphanet] 206 / 7739
11
 (HPO:0002321) Vertigo 58 / 7739
12
 (HPO:0001256) Intellectual disability, mild 141 / 7739
13
 (HPO:0100543) Cognitive impairment 230 / 7739
14
 (HPO:0000478) Abnormality of the eye 126 / 7739
15
 (HPO:0000280) Coarse facial features Frequent [Orphanet] 189 / 7739
16
 (HPO:0000179) Thick lower lip vermilion 72 / 7739
17
 (HPO:0000214) Lip telangiectasia 6 / 7739
18
 (HPO:0012471) Thick vermilion border Frequent [Orphanet] 115 / 7739
19
 (HPO:0007428) Telangiectasia of the oral mucosa 1 / 7739
20
 (HPO:0005280) Depressed nasal bridge Frequent [Orphanet] 381 / 7739
21
 (HPO:0000407) Sensorineural hearing impairment 524 / 7739
22
 (HPO:0008527) Congenital sensorineural hearing impairment 165 / 7739
23
 (HPO:0008625) Severe sensorineural hearing impairment 150 / 7739
24
 (HPO:0000958) Dry skin 152 / 7739
25
 (HPO:0000962) Hyperkeratosis Very frequent [Orphanet] 216 / 7739
26
 (HPO:0011276) Vascular skin abnormality Very frequent [Orphanet] 24 / 7739
27
 (HPO:0001071) Angiokeratoma corporis diffusum 7 / 7739
28
 (HPO:0100585) Telangiectasia of the skin Very frequent [Orphanet] 66 / 7739
29
 (HPO:0000365) Hearing impairment Frequent [Orphanet] 539 / 7739
30
 (HPO:0000360) Tinnitus Frequent [Orphanet] 29 / 7739
31
 (HPO:0003581) Adult onset 117 / 7739
32
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
33
 (HPO:0040078) Axonal degeneration 10 / 7739
34
 (HPO:0002059) Cerebral atrophy 171 / 7739
35
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
36
 (HPO:0006812) White mater abnormalities in the posterior periventricular region 1 / 7739
37
 (OMIM) Conjunctiva shows dilated blood vessels 1 / 7739
38
 (OMIM) Decreased or absent alpha-N-acetylgalactosaminidase activity 1 / 7739
39
 (OMIM) Decreased or absent alpha-N-acetylgalactosaminidase protein 1 / 7739
40
 (OMIM) Diverse tissue cell types (vascular endothelial cells, adipocytes, Schwann cells, leukocytes) have membrane-lined cytoplasmic vacuoles with amorphous and filamentous material 1 / 7739
41
 (OMIM) Enlarged nasal tip 1 / 7739
42
 (OMIM) Fundi show dilated blood vessels with corkscrew-like tortuosity 1 / 7739
43
 (OMIM) Glycoamino aciduria 1 / 7739
44
 (OMIM) Intellectual impairment, mild 3 / 7739
45
 (OMIM) MRI may show atrophy of the cerebrum 1 / 7739
46
 (OMIM) Maculopapular eruption, diffuse 1 / 7739
47
 (OMIM) Meniere syndrome 1 / 7739
48
 (OMIM) Sural nerve biopsy shows decreased density of myelinated fibers and axonal degeneration 1 / 7739
49
 (OMIM) Telangiectasia on lips and oral mucosa 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Kanzaki et al. (1989) described a 46-year-old Japanese woman with disseminated angiokeratoma, and demonstrated numerous cytoplasmic vacuoles in cells of the kidney and skin. Enzyme activities against synthetic and natural substrates were normal in leukocytes and fibroblasts. Her ...
Molecular genetics OMIM In the Japanese woman with disseminated angiokeratoma reported by Kanzaki et al. (1989), Wang et al. (1990, 1994) identified a homozygous mutation in the NAGA gene (104170.0002).

Keulemans et al. (1996) showed by PCR and sequence ...