Alpha-N-acetylgalactosaminidase deficiency type 1

General Information (adopted from Orphanet):

Synonyms, Signs: SCHINDLER DISEASE, TYPE III, INCLUDED
NAGA DEFICIENCY, TYPE III, INCLUDED
NAGA DEFICIENCY, TYPE I ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY, TYPE III, INCLUDED
ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY, TYPE I
NEUROAXONAL DYSTROPHY, SCHINDLER TYPE
Schindler disease type 1
NAGA deficiency type 1
Number of Symptoms 54
OrphanetNr: 79279
OMIM Id: 609241
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: Neonatal
Infancy
[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:0000639) Nystagmus Frequent [Orphanet] 555 / 7739
2
 (HPO:0000486) Strabismus Frequent [Orphanet] 576 / 7739
3
 (HPO:0100704) Cortical visual impairment 28 / 7739
4
 (HPO:0000648) Optic atrophy 238 / 7739
5
 (HPO:0000572) Visual loss Very frequent [Orphanet] 272 / 7739
6
 (HPO:0000365) Hearing impairment Very frequent [Orphanet] 539 / 7739
7
 (HPO:0003474) Sensory impairment Occasional [Orphanet] 54 / 7739
8
 (HPO:0009830) Peripheral neuropathy Occasional [Orphanet] 206 / 7739
9
 (HPO:0002376) Developmental regression 74 / 7739
10
 (HPO:0001347) Hyperreflexia 363 / 7739
11
 (HPO:0001257) Spasticity 251 / 7739
12
 (HPO:0001276) Hypertonia Very frequent [Orphanet] 317 / 7739
13
 (HPO:0000717) Autism Frequent [Orphanet] 108 / 7739
14
 (HPO:0001250) Seizures 1245 / 7739
15
 (HPO:0010864) Intellectual disability, severe 120 / 7739
16
 (HPO:0000763) Sensory neuropathy Occasional [Orphanet] 78 / 7739
17
 (HPO:0004305) Involuntary movements Frequent [Orphanet] 50 / 7739
18
 (HPO:0002141) Gait imbalance Frequent [Orphanet] 55 / 7739
19
 (HPO:0004374) Hemiplegia/hemiparesis Frequent [Orphanet] 158 / 7739
20
 (HPO:0100543) Cognitive impairment Very frequent [Orphanet] 230 / 7739
21
 (HPO:0007256) Abnormal pyramidal signs Very frequent [Orphanet] 116 / 7739
22
 (HPO:0001336) Myoclonus 115 / 7739
23
 (HPO:0000938) Osteopenia 138 / 7739
24
 (HPO:0002240) Hepatomegaly Occasional [Orphanet] 467 / 7739
25
 (HPO:0011276) Vascular skin abnormality Frequent [Orphanet] 24 / 7739
26
 (HPO:0100585) Telangiectasia of the skin Frequent [Orphanet] 66 / 7739
27
 (HPO:0000962) Hyperkeratosis Frequent [Orphanet] 216 / 7739
28
 (HPO:0001638) Cardiomyopathy Occasional [Orphanet] 192 / 7739
29
 (HPO:0001004) Lymphedema Occasional [Orphanet] 62 / 7739
30
 (HPO:0003461) Increased urinary O-linked sialopeptides 5 / 7739
31
 (HPO:0010547) Muscle flaccidity 466 / 7739
32
 (HPO:0001252) Muscular hypotonia Very frequent [Orphanet] 990 / 7739
33
 (HPO:0001324) Muscle weakness Very frequent [Orphanet] 859 / 7739
34
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
35
 (HPO:0003700) Generalized amyotrophy 39 / 7739
36
 (OMIM) Decreased alpha-N-acetylgalactosaminidase protein 2 / 7739
37
 (OMIM) Rapid regression 2 / 7739
38
 (OMIM) Normal early development, up to 8 to 15 months of age 2 / 7739
39
 (OMIM) Increased urinary oligosaccharides 2 / 7739
40
 (HPO:0002334) Abnormality of the cerebellar vermis Occasional [Orphanet] 137 / 7739
41
 (OMIM) Limb contractures by age 4-5 years 2 / 7739
42
 (HPO:0002363) Abnormality of brainstem morphology Very frequent [Orphanet] 14 / 7739
43
 (OMIM) Lack of lysosomal inclusions in visceral organs 2 / 7739
44
 (OMIM) 'Spheroid' inclusions in axons 2 / 7739
45
 (HPO:0012795) Abnormality of the optic disc Frequent [Orphanet] 187 / 7739
46
 (OMIM) No voluntary movement 2 / 7739
47
 (MedDRA:10045555) Unresponsive to stimuli 2 / 7739
48
 (OMIM) Delayed development, after 8-15 months 2 / 7739
49
 (OMIM) Decreased alpha-N-acetylgalactosaminidase activity (less than 2% of control) 2 / 7739
50
 (OMIM) Decorticate posturing 2 / 7739
51
 (OMIM) Atrophy of cerebellum, brainstem, cervical spinal cord 2 / 7739
52
 (OMIM) Neuroaxonal dystrophy 4 / 7739
53
 (HPO:0001522) Death in infancy Occasional [Orphanet] 275 / 7739
54
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 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. 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 ...
Clinical Description OMIM - Schindler Disease, Type I

Van Diggelen et al. (1987, 1988) reported 2 sons of a German couple with remote consanguinity who were affected with type I lysosomal alpha-N-acetylgalactosaminidase deficiency. Starting at age 9 months, the ...
Genotype-Phenotype Correlations OMIM Keulemans et al. (1996) found that the 3 related German boys with type I NAGA deficiency retained residual NAGA activity in fibroblasts that was higher than NAGA activity in 2 patients with the less severe adult-onset Kanzaki disease. ...
Molecular genetics OMIM In the 2 German boys with alpha-N-acetylgalactosaminidase deficiency reported by van Diggelen et al. (1987, 1988), Wang et al. (1990) identified a homozygous glu325-to-lys (E325K) mutation in the NAGA gene (104170.0001). Keulemans et al. (1996) identified a distant ...