Rare Ophthalmology News

Disease Profile

Aspartylglycosaminuria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

E77.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Aspartylglucosaminuria; Aspartylglucosamidase (AGA) deficiency; AGU;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases;

Summary

Aspartylglycosaminuria is a very rare lysosomal storage disease that causes a progressive decline in mental functioning. Infants with aspartylglycosaminuria appear healthy at birth with signs and symptoms beginning around the age of 2 or 3. Major symptoms may include coarse facial features, spine and eye deformities, behavior problems, and intellectual disability. Symptoms result from a deficiency in an enzyme called aspartylglycosaminidase, which leads to an accumulation of a protein called glycoasparagine in the body tissues and increased excretion of this protein in the urine. Aspartylglycosaminuria is inherited in an autosomal recessive fashion and caused by mutations in the AGA gene. It is commonly seen in individuals of Finnish decent.[1][2][3]

Symptoms

Infants with aspartylglycosaminuria appear healthy at birth, and development is typcailly normal throughout childhood. The first sign of this condition, which becomes 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.[3]

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.[3] The skeleton may also become deformed. The spine may be twisted (scoliosis) and the neck may be unusually short. The eyes may also develop cataracts. Behavior problems are common. Lung, heart and blood problems tend to occur in later years.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Aspartylglycosaminuria. Click on the link to view a sample search on this topic.

          References

          1. Froissart R & Maire I. Aspartylglucosaminuria. Orphanet. February 2005; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93. Accessed 8/17/2011.
          2. Aspartylglycosaminuria . National Organization for Rare Disorders (NORD). 2004; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/918/viewAbstract. Accessed 8/17/2011.
          3. Aspartylglucosaminuria. Genetics Home Reference. December 2008; https://ghr.nlm.nih.gov/condition/aspartylglucosaminuria. Accessed 8/17/2011.

          Rare Ophthalmology News

          Medical Terms Other Names
          Learn More:
          HPO ID
          80%-99% of people have these symptoms
          Abnormality of amino acid metabolism
          0004337
          Aspartylglucosaminuria
          High urine aspartylglucosamine levels
          0012068
          Delayed speech and language development
          Deficiency of speech development
          Delayed language development
          Delayed speech
          Delayed speech acquisition
          Delayed speech development
          Impaired speech and language development
          Impaired speech development
          Language delay
          Language delayed
          Language development deficit
          Late-onset speech development
          Poor language development
          Speech and language delay
          Speech and language difficulties
          Speech delay

          [ more ]

          0000750
          Dyskinesia
          Disorder of involuntary muscle movements
          0100660
          Gingival overgrowth
          Gum enlargement
          0000212
          Hypertelorism
          Wide-set eyes
          Widely spaced eyes

          [ more ]

          0000316
          Intellectual disability
          Mental deficiency
          Mental retardation
          Mental retardation, nonspecific
          Mental-retardation

          [ more ]

          0001249
          Large face
          Big face
          0100729
          Mandibular prognathia
          Big lower jaw
          Increased projection of lower jaw
          Increased size of lower jaw
          Large lower jaw
          Prominent chin
          Prominent lower jaw

          [ more ]

          0000303
          Microtia
          Small ears
          Underdeveloped ears

          [ more ]

          0008551
          Neurological speech impairment
          Speech disorder
          Speech impairment
          Speech impediment

          [ more ]

          0002167
          Scoliosis
          0002650
          Short nose
          Decreased length of nose
          Shortened nose

          [ more ]

          0003196
          Thick vermilion border
          Full lips
          Increased volume of lip
          Plump lips
          Prominent lips
          Thick lips

          [ more ]

          0012471
          Umbilical hernia
          0001537
          Wide nasal bridge
          Broad nasal bridge
          Broad nasal root
          Broadened nasal bridge
          Increased breadth of bridge of nose
          Increased breadth of nasal bridge
          Increased width of bridge of nose
          Increased width of nasal bridge
          Nasal bridge broad
          Wide bridge of nose
          Widened nasal bridge

          [ more ]

          0000431
          30%-79% of people have these symptoms
          Abnormal cortical bone morphology
          0003103
          Abnormality of the ulna
          0002997
          Anterior beaking of lumbar vertebrae
          0008430
          Carious teeth
          Dental cavities
          Tooth cavities
          Tooth decay

          [ more ]

          0000670
          Coarse facial features
          Coarse facial appearance
          0000280
          Macroglossia
          Abnormally large tongue
          Increased size of tongue
          Large tongue

          [ more ]

          0000158
          Macroorchidism
          Large testis
          0000053
          Pectus carinatum
          Pigeon chest
          0000768
          Thickened calvaria
          Increased thickness of skull cap
          Thickened skull cap

          [ more ]

          0002684
          5%-29% of people have these symptoms
          Arthritis
          Joint inflammation
          0001369
          Chronic otitis media
          Chronic infections of the middle ear
          0000389
          Delayed skeletal maturation
          Delayed bone maturation
          Delayed skeletal development

          [ more ]

          0002750
          Hepatomegaly
          Enlarged liver
          0002240
          Inguinal hernia
          0000023
          Joint stiffness
          Stiff joint
          Stiff joints

          [ more ]

          0001387
          Malabsorption
          Intestinal malabsorption
          0002024
          Pes planus
          Flat feet
          Flat foot

          [ more ]

          0001763
          Recurrent respiratory infections
          Frequent respiratory infections
          Multiple respiratory infections
          respiratory infections, recurrent
          Susceptibility to respiratory infections

          [ more ]

          0002205
          Seizure
          0001250
          Sleep disturbance
          Difficulty sleeping
          Trouble sleeping

          [ more ]

          0002360
          Splenomegaly
          Increased spleen size
          0001744
          Vascular skin abnormality
          0011276
          Percent of people who have these symptoms is not available through HPO
          Abnormality of metabolism/homeostasis
          Laboratory abnormality
          Metabolism abnormality

          [ more ]

          0001939
          Acne
          0001061
          Angiokeratoma corporis diffusum
          0001071
          Anteverted nares
          Nasal tip, upturned
          Upturned nasal tip
          Upturned nose
          Upturned nostrils

          [ more ]

          0000463
          Autosomal recessive inheritance
          0000007
          Beaking of vertebral bodies
          0004568
          Brachycephaly
          Short and broad skull
          0000248
          Broad face
          Increased breadth of face
          Increased width of face
          Wide face

          [ more ]

          0000283
          Cataract
          Clouding of the lens of the eye
          Cloudy lens

          [ more ]

          0000518
          Cerebral atrophy
          Degeneration of cerebrum
          0002059
          Decreased prothrombin time
          0032198