Aspartylglucosaminuria

General Information (adopted from Orphanet):

Synonyms, Signs: GLYCOSYLASPARAGINASE DEFICIENCY
AGA DEFICIENCY
ASPARTYLGLYCOSAMINURIA
GLYCOASPARAGINASE
AGU
aspartylglucosaminidase deficiency
Number of Symptoms 86
OrphanetNr: 93
OMIM Id: 208400
ICD-10: E77.1
UMLs: C0268225
C2931840
MeSH: C538402
D054880
MedDRA: 10068220
Snomed: 54954004

Prevalence, inheritance and age of onset:

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

Disease classification (adopted from Orphanet):

Parent Diseases: Developmental anomaly of metabolic origin
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Lysosomal disease with epilepsy
 -Rare neurologic disease
Lysosomal storage disease with skeletal involvement
 -Rare bone disease
 -Rare genetic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
Oligosaccharidosis
 -Rare developmental defect during embryogenesis
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0002014) Diarrhea 225 / 7739
2
 (HPO:0000316) Hypertelorism Very frequent [Orphanet] 644 / 7739
3
 (HPO:0000518) Cataract 454 / 7739
4
 (HPO:0002205) Recurrent respiratory infections Occasional [Orphanet] 254 / 7739
5
 (HPO:0001609) Hoarse voice 34 / 7739
6
 (HPO:0004322) Short stature 1232 / 7739
7
 (HPO:0012068) Aspartylglucosaminuria 1 / 7739
8
 (HPO:0001653) Mitral regurgitation 64 / 7739
9
 (HPO:0002719) Recurrent infections 107 / 7739
10
 (HPO:0001922) Vacuolated lymphocytes 13 / 7739
11
 (HPO:0001875) Neutropenia 83 / 7739
12
 (HPO:0001939) Abnormality of metabolism/homeostasis Very frequent [Orphanet] 328 / 7739
13
 (HPO:0000158) Macroglossia Frequent [Orphanet] 119 / 7739
14
 (HPO:0001252) Muscular hypotonia 990 / 7739
15
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
16
 (HPO:0010547) Muscle flaccidity 466 / 7739
17
 (HPO:0001324) Muscle weakness 859 / 7739
18
 (HPO:0001257) Spasticity 251 / 7739
19
 (HPO:0000708) Behavioral abnormality Occasional [Orphanet] 212 / 7739
20
 (HPO:0002376) Developmental regression 74 / 7739
21
 (HPO:0001249) Intellectual disability 1089 / 7739
22
 (HPO:0002360) Sleep disturbance Occasional [Orphanet] 113 / 7739
23
 (HPO:0000750) Delayed speech and language development 197 / 7739
24
 (HPO:0002167) Neurological speech impairment Very frequent [Orphanet] 308 / 7739
25
 (HPO:0100022) Abnormality of movement Very frequent [Orphanet] 129 / 7739
26
 (HPO:0001250) Seizures Occasional [Orphanet] 1245 / 7739
27
 (HPO:0001327) Photomyoclonic seizures 125 / 7739
28
 (HPO:0001763) Pes planus Occasional [Orphanet] 176 / 7739
29
 (HPO:0002997) Abnormality of the ulna Frequent [Orphanet] 75 / 7739
30
 (HPO:0000303) Mandibular prognathia Very frequent [Orphanet] 179 / 7739
31
 (HPO:0002738) Hypoplastic frontal sinuses 6 / 7739
32
 (HPO:0000248) Brachycephaly 222 / 7739
33
 (HPO:0004437) Cranial hyperostosis Frequent [Orphanet] 55 / 7739
34
 (HPO:0000252) Microcephaly 832 / 7739
35
 (HPO:0002684) Thickened calvaria 32 / 7739
36
 (HPO:0000768) Pectus carinatum Frequent [Orphanet] 136 / 7739
37
 (HPO:0003312) Abnormal form of the vertebral bodies Frequent [Orphanet] 172 / 7739
38
 (HPO:0004568) Beaking of vertebral bodies 19 / 7739
39
 (HPO:0000926) Platyspondyly 150 / 7739
40
 (HPO:0002808) Kyphosis 289 / 7739
41
 (HPO:0002650) Scoliosis Very frequent [Orphanet] 705 / 7739
42
 (HPO:0003302) Spondylolisthesis 14 / 7739
43
 (HPO:0003304) Spondylolysis 11 / 7739
44
 (HPO:0003103) Abnormal cortical bone morphology Frequent [Orphanet] 38 / 7739
45
 (HPO:0001388) Joint laxity 117 / 7739
46
 (HPO:0001387) Joint stiffness Occasional [Orphanet] 322 / 7739
47
 (HPO:0100769) Synovitis Occasional [Orphanet] 86 / 7739
48
 (HPO:0000943) Dysostosis multiplex 22 / 7739
49
 (HPO:0002750) Delayed skeletal maturation 250 / 7739
50
 (HPO:0002756) Pathologic fracture 30 / 7739
51
 (HPO:0002024) Malabsorption Occasional [Orphanet] 142 / 7739
52
 (HPO:0002240) Hepatomegaly Occasional [Orphanet] 467 / 7739
53
 (HPO:0006568) Increased hepatic glycogen content Very frequent [Orphanet] 34 / 7739
54
 (HPO:0001744) Splenomegaly Occasional [Orphanet] 337 / 7739
55
 (HPO:0001537) Umbilical hernia Very frequent [Orphanet] 206 / 7739
56
 (HPO:0004299) Hernia of the abdominal wall Occasional [Orphanet] 176 / 7739
57
 (HPO:0000053) Macroorchidism Frequent [Orphanet] 18 / 7739
58
 (HPO:0001999) Abnormal facial shape Very frequent [Orphanet] 169 / 7739
59
 (HPO:0000283) Broad face 12 / 7739
60
 (HPO:0000280) Coarse facial features Frequent [Orphanet] 189 / 7739
61
 (HPO:0100729) Large face Very frequent [Orphanet] 19 / 7739
62
 (HPO:0000179) Thick lower lip vermilion 72 / 7739
63
 (HPO:0012471) Thick vermilion border Very frequent [Orphanet] 115 / 7739
64
 (HPO:0000168) Abnormality of the gingiva Very frequent [Orphanet] 51 / 7739
65
 (HPO:0000164) Abnormality of the teeth Frequent [Orphanet] 291 / 7739
66
 (HPO:0000670) Carious teeth Frequent [Orphanet] 145 / 7739
67
 (HPO:0000154) Wide mouth 137 / 7739
68
 (HPO:0000463) Anteverted nares 305 / 7739
69
 (HPO:0005280) Depressed nasal bridge 381 / 7739
70
 (HPO:0003196) Short nose Very frequent [Orphanet] 264 / 7739
71
 (HPO:0000445) Wide nose Very frequent [Orphanet] 190 / 7739
72
 (HPO:0000389) Chronic otitis media Occasional [Orphanet] 64 / 7739
73
 (HPO:0008772) Aplasia/Hypoplasia of the external ear Very frequent [Orphanet] 67 / 7739
74
 (HPO:0000924) Abnormality of the skeletal system Occasional [Orphanet] 114 / 7739
75
 (HPO:0001061) Acne 33 / 7739
76
 (HPO:0011276) Vascular skin abnormality Occasional [Orphanet] 24 / 7739
77
 (HPO:0001071) Angiokeratoma corporis diffusum 7 / 7739
78
 (HPO:0100790) Hernia 9 / 7739
79
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
80
 (HPO:0002059) Cerebral atrophy 171 / 7739
81
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
82
 (OMIM) Crystal-like lens opacity 1 / 7739
83
 (OMIM) Decreased prothrombin time 1 / 7739
84
 (OMIM) Dysostosis multiplex, mild (in some patients) 5 / 7739
85
 (OMIM) Flattening and anterior beaking of vertebral bodies 1 / 7739
86
 (OMIM) Little to absent aspartylglucosaminuria activity 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Aspartylglucosaminuria is a severe autosomal recessive lysosomal storage disorder that involves the central nervous system and causes skeletal abnormalities as well as connective tissue lesions. The most characteristic feature is progressive mental retardation. The disorder is caused by ...
Diagnosis OMIM Mononen et al. (1994) described a fluorometric glycosylasparaginase assay for neonatal screening for AGU.

Zlotogora et al. (1997) stated that the clinical diagnosis of AGU is difficult, in particular early in the course of the disease; ...
Clinical Description OMIM Aspartylglucosaminuria was first reported by Jenner and Pollitt (1967) and Pollitt et al. (1968), who found urinary excretion of abnormal amounts of 2-acetamido-1-(beta-L-aspartamido)-1,2-dideoxyglucose in a 32-year-old female and her 20-year-old brother with mental retardation. An enzyme responsible for ...
Molecular genetics OMIM In Finnish patients with aspartylglucosaminuria, Ikonen et al. (1991) and Fisher and Aronson (1991) independently identified homozygosity for a cys163-to-ser (C163S; 613228.0001) mutation in the AGA gene. The C163S mutation is responsible for 98% of the cases of ...
Population genetics OMIM Aspartylglucosaminuria occurs worldwide, but is enriched in the Finnish population (Arvio and Arvio, 2002).

Palo and Mattsson (1970) estimated that there are at least 130 cases in the total population of 4.5 million in Finland. ...