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Aspartylglycosaminuria(AGU)

MedGen UID:
78649
Concept ID:
C0268225
Disease or Syndrome
Synonyms: AGA deficiency; AGU; Aspartylglucos-amidase (AGA) deficiency; Aspartylglucos-aminuria; GLYCOASPARAGINASE; Glycosylasparaginase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Aspartylglycosylaminase deficiency (54954004); Aspartylglucosaminuria (54954004); Aspartylglycosaminuria (54954004); Aspartylglucosaminidase deficiency (54954004)
 
Gene (location): AGA (4q34.3)
OMIM®: 208400

Definition

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 deficient activity of the lysosomal enzyme glycosylasparaginase, which results in body fluid and tissue accumulation of a series of glycoasparagines, i.e., glycoconjugates with an aspartylglucosamine moiety at the reducing end. AGU belongs to the group of disorders commonly referred to as the Finnish disease heritage (summary by Mononen et al., 1993 and Arvio and Arvio, 2002). [from OMIM]

Additional description

From GHR
Aspartylglucosaminuria is a condition that causes a progressive decline in mental functioning. Infants with aspartylglucosaminuria appear healthy at birth, and development is typically normal throughout early childhood. The first sign of this condition, evident around the age of 2 or 3, is usually delayed speech. Mild intellectual disability then becomes apparent, and learning occurs at a slowed pace. Intellectual disability progressively worsens in adolescence. Most people with this disorder lose much of the speech they have learned, and affected adults usually have only a few words in their vocabulary. Adults with aspartylglucosaminuria may develop seizures or problems with movement. People with this condition may also have bones that become progressively weak and prone to fracture (osteoporosis), an unusually large range of joint movement (hypermobility), and loose skin. Affected individuals tend to have a characteristic facial appearance that includes widely spaced eyes (ocular hypertelorism), small ears, and full lips. The nose is short and broad and the face is usually square-shaped. Children with this condition may be tall for their age, but lack of a growth spurt in puberty typically causes adults to be short. Affected children also tend to have frequent upper respiratory infections. Individuals with aspartylglucosaminuria usually survive into mid-adulthood.  http://ghr.nlm.nih.gov/condition/aspartylglucosaminuria

Clinical features

Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Macroorchidism
MedGen UID:
504320
Concept ID:
CN000053
Finding
The presence of abnormally large testes.
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Hypoplastic frontal sinuses
MedGen UID:
376917
Concept ID:
C1850969
Finding
Anteverted nares
MedGen UID:
339940
Concept ID:
C1853244
Finding
Coarse facial features
MedGen UID:
381459
Concept ID:
C1854600
Finding
Thickened calvaria
MedGen UID:
347516
Concept ID:
C1857647
Finding
Broad face
MedGen UID:
349223
Concept ID:
C1859680
Finding
Carious teeth
MedGen UID:
401327
Concept ID:
C1867882
Finding
Craniofacial hyperostosis
MedGen UID:
358122
Concept ID:
C1868085
Finding
Large face
MedGen UID:
411263
Concept ID:
C2748652
Finding
Wide mouth
MedGen UID:
504368
Concept ID:
CN000150
Finding
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Abnormality of the tongue
MedGen UID:
446339
Concept ID:
CN000153
Finding
Any abnormality of the tongue.
Macroglossia
MedGen UID:
504371
Concept ID:
CN000154
Finding
Increased length and width of the tongue.
Thick lower lip vermilion
MedGen UID:
504381
Concept ID:
CN000174
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Gingival overgrowth
MedGen UID:
504394
Concept ID:
CN000205
Finding
Hyperplasia of the gingiva (FMA:59762, that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Brachycephaly
MedGen UID:
504407
Concept ID:
CN000240
Finding
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Mandibular prognathia
MedGen UID:
427817
Concept ID:
CN000285
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Short nose
MedGen UID:
505478
Concept ID:
CN002885
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Depressed nasal bridge
MedGen UID:
446656
Concept ID:
CN004681
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Cataract
MedGen UID:
368085
Concept ID:
C1962983
Finding
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Abnormality of the outer ear
MedGen UID:
446349
Concept ID:
CN000332
Finding
An abnormality of the external ear.
Otitis media
MedGen UID:
504428
Concept ID:
CN000363
Finding
Inflammation or infection of the middle ear.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Cognitive impairment
MedGen UID:
383844
Concept ID:
C1856145
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Delayed speech and language development
MedGen UID:
504583
Concept ID:
CN000706
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Cerebral atrophy
MedGen UID:
505074
Concept ID:
CN001862
Finding
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Neurological speech impairment
MedGen UID:
446437
Concept ID:
CN001964
Finding
Sleep disturbance
MedGen UID:
505212
Concept ID:
CN002143
Finding
An abnormality of sleep including such phenomena as 1) insomnia/hypersomnia, 2) non-restorative sleep, 3) sleep schedule disorder, 4) excessive daytime somnolence, 5) sleep apnea, and 6) restlessness.
Abnormality of movement
MedGen UID:
506445
Concept ID:
CN116921
Finding
An abnormality of movement with a neurological basis characterized by changes in coordination and speed of voluntary movements.
Kyphosis
MedGen UID:
335104
Concept ID:
C1845112
Finding
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Hypoplastic frontal sinuses
MedGen UID:
376917
Concept ID:
C1850969
Finding
Thickened calvaria
MedGen UID:
347516
Concept ID:
C1857647
Finding
Platyspondyly
MedGen UID:
355353
Concept ID:
C1865023
Finding
Craniofacial hyperostosis
MedGen UID:
358122
Concept ID:
C1868085
Finding
Brachycephaly
MedGen UID:
504407
Concept ID:
CN000240
Finding
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Mandibular prognathia
MedGen UID:
427817
Concept ID:
CN000285
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Pectus carinatum
MedGen UID:
504592
Concept ID:
CN000722
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Dysostosis multiplex
MedGen UID:
504655
Concept ID:
CN000882
Finding
Arthritis
MedGen UID:
504815
Concept ID:
CN001254
Finding
Inflammation of a joint.
Limitation of joint mobility
MedGen UID:
446405
Concept ID:
CN001260
Finding
A reduction in the freedom of movement of one or more joints.
Joint laxity
MedGen UID:
504825
Concept ID:
CN001270
Finding
Lack of stability of a joint.
Scoliosis
MedGen UID:
427922
Concept ID:
CN002409
Finding
The presence of an abnormal lateral curvature of the spine.
Delayed skeletal maturation
MedGen UID:
505344
Concept ID:
CN002495
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Pathologic fracture
MedGen UID:
505347
Concept ID:
CN002501
Finding
A pathologic fracture occurs when a bone breaks in an area that is weakened secondary to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Abnormality of the ulna
MedGen UID:
446463
Concept ID:
CN002710
Finding
An abnormality of the ulna bone of the forearm.
Abnormal cortical bone morphology
MedGen UID:
446470
Concept ID:
CN002798
Finding
An abnormality of compact bone (also known as cortical bone), which forms the dense surface of bones.
Spondylolisthesis
MedGen UID:
505511
Concept ID:
CN002979
Finding
Complete bilateral fractures of the pars interarticularis resulting in the anterior slippage of the vertebra.
Spondylolysis
MedGen UID:
505512
Concept ID:
CN002980
Finding
Spondylolysis is an osseous defect of the pars interarticularis, thought to be a developmental or acquired stress fracture secondary to chronic low-grade trauma.
Beaking of vertebral bodies
MedGen UID:
428472
Concept ID:
CN004052
Finding
Anterior tongue-like protrusions of the vertebral bodies.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Diarrhea
MedGen UID:
368098
Concept ID:
C1963091
Finding
Malabsorption
MedGen UID:
368423
Concept ID:
C1963165
Finding
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Acne
MedGen UID:
504704
Concept ID:
CN000996
Finding
A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).
Angiokeratoma corporis diffusum
MedGen UID:
504709
Concept ID:
CN001006
Finding
Hoarse voice
MedGen UID:
504872
Concept ID:
CN001465
Finding
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Angiokeratoma corporis diffusum
MedGen UID:
504709
Concept ID:
CN001006
Finding
Mitral regurgitation
MedGen UID:
504894
Concept ID:
CN001505
Finding
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
Neutropenia
MedGen UID:
18030
Concept ID:
C0027947
Disease or Syndrome
An abnormal decrease in the number of neutrophils, a type of white blood cell.
Vacuolated lymphocytes
MedGen UID:
332307
Concept ID:
C1836855
Finding
The determination of the amount of vacuolated lymphocytes present in a sample.
Abnormality of metabolism/homeostasis
MedGen UID:
446429
Concept ID:
CN001754
Finding
Aspartylglucosaminuria
MedGen UID:
506661
Concept ID:
CN167794
Finding
Excretion of excess amounts of aspartylglucosamine in the urine.
Recurrent respiratory infections
MedGen UID:
400943
Concept ID:
C1866203
Finding
Neutropenia
MedGen UID:
18030
Concept ID:
C0027947
Disease or Syndrome
An abnormal decrease in the number of neutrophils, a type of white blood cell.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Vacuolated lymphocytes
MedGen UID:
332307
Concept ID:
C1836855
Finding
The determination of the amount of vacuolated lymphocytes present in a sample.
Recurrent respiratory infections
MedGen UID:
400943
Concept ID:
C1866203
Finding
Macroglossia
MedGen UID:
504371
Concept ID:
CN000154
Finding
Increased length and width of the tongue.
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Hernia
MedGen UID:
452018
Concept ID:
CN117680
Finding
Pes planus
MedGen UID:
427894
Concept ID:
CN001603
Finding
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Abnormality of the ulna
MedGen UID:
446463
Concept ID:
CN002710
Finding
An abnormality of the ulna bone of the forearm.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGAspartylglycosaminuria

Recent clinical studies

Etiology

Dunder U, Valtonen P, Kelo E, Mononen I
J Inherit Metab Dis 2010 Oct;33(5):611-7. Epub 2010 Jul 6 doi: 10.1007/s10545-010-9158-7. [Epub ahead of print] PMID: 20607610
Risley JM, Huang DH, Kaylor JJ, Malik JJ, Xia YQ, York WM
Arch Biochem Biophys 2001 Jul 15;391(2):165-70. doi: 10.1006/abbi.2001.2416. PMID: 11437347
Kallinen J, Marin K, Heinonen S, Mannermaa A, Palotie A, Ryynänen M
BJOG 2001 May;108(5):505-9. PMID: 11368137
Mononen I, Heisterkamp N, Kaartinen V, Mononen T, Williams JC, Groffen J
J Biol Chem 1992 Feb 15;267(5):3196-9. PMID: 1737774
Mononen T, Mononen I, Matilainen R, Airaksinen E
Hum Genet 1991 Jul;87(3):266-8. PMID: 1864600

Diagnosis

Mononen I, Kaartinen V, Mononen T
Scand J Clin Lab Invest Suppl 1988;191:7-11. PMID: 3247584
Mononen I, Kaartinen V, Mononen T
J Inherit Metab Dis 1988;11(2):194-8. PMID: 3139932
Näntö-Salonen K, Larjava H, Säämanen AM, Heino J, Penttinen R, Pelliniemi LJ, Tammi M
Connect Tissue Res 1987;16(4):367-76. PMID: 3132350
Maury CP
Clin Chem 1981 Dec;27(12):2058-60. PMID: 7307258
Maury P, Palo J
Clin Sci (Lond) 1980 Feb;58(2):165-8. PMID: 7357836

Therapy

Dunder U, Valtonen P, Kelo E, Mononen I
J Inherit Metab Dis 2010 Oct;33(5):611-7. Epub 2010 Jul 6 doi: 10.1007/s10545-010-9158-7. [Epub ahead of print] PMID: 20607610
Mononen I, Heisterkamp N, Dunder U, Romppanen EL, Noronkoski T, Kuronen I, Groffen J
FASEB J 1995 Mar;9(5):428-33. PMID: 7896015
Delahunty CM, Ankener W, Brainerd S, Nickerson DA, Mononen IT
Clin Chem 1995 Jan;41(1):59-61. PMID: 7813081
Mononen T, Mononen I, Matilainen R, Airaksinen E
Hum Genet 1991 Jul;87(3):266-8. PMID: 1864600
Ockerman PA, Hultberg B
J Ment Defic Res 1972 Sep-Dec;16(3):153-9. PMID: 4671957

Prognosis

Kaartinen V, Mononen I, Voncken JW, Noronkoski T, Gonzalez-Gomez I, Heisterkamp N, Groffen J
Nat Med 1996 Dec;2(12):1375-8. PMID: 8946839
Bonnaure-Mallet M, Loiseau-Corvez MN, Goasguen J, Apiou J, Jezequel C
J Oral Pathol Med 1991 May;20(5):237-40. PMID: 2066874

Clinical prediction guides

Dunder U, Valtonen P, Kelo E, Mononen I
J Inherit Metab Dis 2010 Oct;33(5):611-7. Epub 2010 Jul 6 doi: 10.1007/s10545-010-9158-7. [Epub ahead of print] PMID: 20607610
Näntö-Salonen K, Larjava H, Aalto M, Kivimäki T
Clin Chim Acta 1985 Mar 15;146(2-3):111-8. PMID: 3987044
Näntö-Salonen K, Halme T, Penttinen R, Langevelde FV, Vis RD, Alfthan G
J Inherit Metab Dis 1985;8(4):212-8. PMID: 3939546
Näntö-Salonen K, Pelliniemi LJ, Autio S, Kivimäki T, Rapola J, Penttinen R
Lab Invest 1984 Oct;51(4):464-8. PMID: 6592395
Gehler J, Sewell AC, Becker C, Spranger J, Hartmann J
J Inherit Metab Dis 1981;4(4):229-30. PMID: 6796777

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