Format

Send to:

Choose Destination

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
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Aspartylglycosylaminase deficiency (54954004); Aspartylglucosaminuria (54954004); Aspartylglycosaminuria (54954004); Aspartylglucosaminidase deficiency (54954004)
 
Gene (location): AGA (4q34.3)
OMIM®: 208400
HPO: HP:0012068

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.  https://ghr.nlm.nih.gov/condition/aspartylglucosaminuria

Clinical features

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 ulna
MedGen UID:
446463
Concept ID:
CN002710
Finding
An abnormality of the ulna bone of the forearm.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Finding
backflow of blood from the left ventricle into the left atrium, owing to imperfect functioning of the mitral valve.
Angiokeratoma corporis diffusum
MedGen UID:
504709
Concept ID:
CN001006
Finding
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Height greater than two standard deviations below the mean of the appropriate reference population for the age and sex of the individual.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Diarrhea
MedGen UID:
368098
Concept ID:
C1963091
Finding
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
External ear malformation
MedGen UID:
335428
Concept ID:
C1846460
Anatomical Abnormality
An abnormality of the external ear.
Otitis media
MedGen UID:
504428
Concept ID:
CN000363
Finding
Inflammation or infection of the middle ear.
Abnormality of movement
MedGen UID:
10113
Concept ID:
C0026650
Disease or Syndrome
Imagine if parts of your body moved when you didn't want them to. If you have a movement disorder, you experience these kinds of impaired movement. Dyskinesia is abnormal uncontrolled movement and is a common symptom of many movement disorders. Tremors are a type of dyskinesia. . Nerve diseases cause many movement disorders, such as Parkinson's disease. Other causes include injuries, autoimmune diseases, infections and certain medicines. Many movement disorders are inherited, which means they run in families. Treatment varies by disorder. Medicine can cure some disorders. Others get better when an underlying disease is treated. Often, however, there is no cure. In that case, the goal of treatment is to improve symptoms and relieve pain.
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Seizures are symptoms of a brain problem. They happen because of sudden, abnormal electrical activity in the brain. When people think of seizures, they often think of convulsions in which a person's body shakes rapidly and uncontrollably. Not all seizures cause convulsions. There are many types of seizures and some have mild symptoms. Seizures fall into two main groups. Focal seizures, also called partial seizures, happen in just one part of the brain. Generalized seizures are a result of abnormal activity on both sides of the brain. . Most seizures last from 30 seconds to 2 minutes and do not cause lasting harm. However, it is a medical emergency if seizures last longer than 5 minutes or if a person has many seizures and does not wake up between them. Seizures can have many causes, including medicines, high fevers, head injuries and certain diseases. People who have recurring seizures due to a brain disorder have epilepsy. . NIH: National Institute of Neurological Disorders and Stroke.
Neurological speech impairment
MedGen UID:
11531
Concept ID:
C0037822
Disease or Syndrome
A term referring to disorders characterized by the disruption of normal speech. It includes stuttering, lisps, dysarthria and voice disorders.
Brain atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Sign or Symptom
A degree of language development that is significantly below the norm for a child of a specified age.
Loss of developmental milestones
MedGen UID:
373115
Concept ID:
C1836550
Finding
Loss of developmental skills, as manifested by loss of developmental milestones.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Cognitive impairment
MedGen UID:
451875
Concept ID:
CN117436
Finding
Abnormality in the process of thought including the ability to process information.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Vacuolated lymphocytes
MedGen UID:
332307
Concept ID:
C1836855
Finding
The presence of clear, sharply defined vacuoles in the lymphocyte cytoplasm.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Diarrhea
MedGen UID:
368098
Concept ID:
C1963091
Finding
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A diminution of the skeletal muscle tone marked by a diminished resistance to passive stretching.
Macroglossia
MedGen UID:
504371
Concept ID:
CN000154
Finding
Increased length and width of the tongue.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Vacuolated lymphocytes
MedGen UID:
332307
Concept ID:
C1836855
Finding
The presence of clear, sharply defined vacuoles in the lymphocyte cytoplasm.
Otitis media
MedGen UID:
504428
Concept ID:
CN000363
Finding
Inflammation or infection of the middle ear.
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).
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
Aspartylglucosaminuria
MedGen UID:
506661
Concept ID:
CN167794
Finding
Excretion of excess amounts of aspartylglucosamine in the urine.
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.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Deformities of the SPINE characterized by an exaggerated convexity of the vertebral column. The forward bending of the thoracic region usually is more than 40 degrees. This deformity sometimes is called round back or hunchback.
Hurler syndrome
MedGen UID:
39698
Concept ID:
C0086795
Disease or Syndrome
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having either severe or attenuated MPS I, a distinction that influences therapeutic options. Severe MPS I. Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth decreases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life. Attenuated MPS I. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
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.
Scoliosis
MedGen UID:
195976
Concept ID:
C0700208
Finding
The presence of an abnormal lateral curvature of the spine.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Beaking of vertebral bodies
MedGen UID:
341588
Concept ID:
C1856599
Finding
Anterior tongue-like protrusions of the vertebral bodies.
Limitation of joint mobility
MedGen UID:
341696
Concept ID:
C1857108
Finding
A reduction in the freedom of movement of one or more joints.
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Hypoplastic frontal sinuses
MedGen UID:
349225
Concept ID:
C1859682
Finding
Underdevelopment of frontal sinus.
Craniofacial hyperostosis
MedGen UID:
358122
Concept ID:
C1868085
Finding
Excessive growth of the craniofacial bones.
Abnormal cortical bone morphology
MedGen UID:
867376
Concept ID:
C4021741
Anatomical Abnormality
An abnormality of compact bone (also known as cortical bone), which forms the dense surface of bones.
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.
Arthritis
MedGen UID:
504815
Concept ID:
CN001254
Finding
Inflammation of a joint.
Joint laxity
MedGen UID:
504825
Concept ID:
CN001270
Finding
Lack of stability of a joint.
Abnormality of the ulna
MedGen UID:
446463
Concept ID:
CN002710
Finding
An abnormality of the ulna bone of the forearm.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Abnormality of the tongue
MedGen UID:
451075
Concept ID:
C0878638
Sign or Symptom
Any abnormality of the tongue.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
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).
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Broad face
MedGen UID:
349223
Concept ID:
C1859680
Finding
Bizygomatic (upper face) and bigonial (lower face) width greater than 2 standard deviations above the mean (objective); or an apparent increase in the width of the face (subjective).
Hypoplastic frontal sinuses
MedGen UID:
349225
Concept ID:
C1859682
Finding
Underdevelopment of frontal sinus.
Carious teeth
MedGen UID:
401327
Concept ID:
C1867882
Finding
Craniofacial hyperostosis
MedGen UID:
358122
Concept ID:
C1868085
Finding
Excessive growth of the craniofacial bones.
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).
Macroglossia
MedGen UID:
504371
Concept ID:
CN000154
Finding
Increased length and width of the tongue.
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.
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).
Hernia
MedGen UID:
6816
Concept ID:
C0019270
Finding
A hernia happens when part of an internal organ or tissue bulges through a weak area of muscle. Most hernias are in the abdomen. There are several types of hernias, including. - Inguinal, in the groin. This is the the most common type. - Umbilical, around the belly button. - Incisional, through a scar. - Hiatal, a small opening in the diaphragm that allows the upper part of the stomach to move up into the chest. - Congenital diaphragmatic, a birth defect that needs surgery. Hernias are common. They can affect men, women, and children. A combination of muscle weakness and straining, such as with heavy lifting, might contribute. Some people are born with weak abdominal muscles and may be more likely to get a hernia. Treatment is usually surgery to repair the opening in the muscle wall. Untreated hernias can cause pain and health problems.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
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

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAspartylglycosaminuria

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. 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, Mononen T, Ylikangas P, Kaartinen V, Savolainen K
Clin Chem 1994 Mar;40(3):385-8. PMID: 8131272
Mononen I, Fisher KJ, Kaartinen V, Aronson NN Jr
FASEB J 1993 Oct;7(13):1247-56. PMID: 8405810
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

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. 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

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. 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

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center