- Donate
- Understanding Rare Disease
- Living with a Rare Disease
- Community Support
- Advancing Research
- Driving Policy
- Get Involved
- Rare Disease News
- Resource Library
- About Us
- For Clinicians & Researchers
- For Patient Organizations
Last updated: 6/5/2025
Years published: 2025
NORD gratefully acknowledges Christy Capestany Duran, MD (IMG) and Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for the preparation of this report.
Summary
Aspartylglucosaminuria (AGU) is a rare genetic disorder that affects the body’s ability to break down certain sugars due to a deficiency of the enzyme glycosylasparaginase. Without this enzyme, sugars build up in the body which can cause various health issues, especially affecting brain function. The signs and symptoms of AGU usually become noticeable in childhood and progress over time.
Babies appear normal at birth but during childhood (ages 0 to 12) they may learn slowly, have mild intellectual disabilities, be taller and have a larger head compared to their peers. During puberty and early adolescence (ages 13 to 25), learning difficulties become more severe and some skills may decline. Many adults with this condition have severe intellectual disabilities and may need help with daily tasks, often becoming quieter and, in some people, aggressive if disturbed. Typically, adults with AGU also have shorter stature and smaller heads.
Aspartylglucosaminuria (AGU) is caused by disease causing changes (pathogenic variants) in the AGA gene. Inheritance is autosomal recessive.
Most people affected with AGU are of Finnish descent.
Currently, there is no cure for AGU, but early diagnosis and supportive care can improve the quality of life for affected individuals. Treatment primarily focuses on managing symptoms and providing support. Researchers are exploring potential new therapies, including enzyme replacement options.
In the 2023 revision of the Nosology of Genetic Skeletal Disorders, aspartylglucosaminuria is referred to as AGA-related aspartylglucosaminuria and included in the lysosomal storage diseases (LSDs) with skeletal involvement group. LSDs are a group of inherited metabolic disorders caused by deficiencies within lysosomes, the small, sac-like structures within cells that contain enzymes responsible for breaking down waste materials, cellular debris and other substances. The enzyme deficiencies in LSDs result in the buildup of undegraded substances in cells and tissues, potentially causing organ damage and other health problems.1-4
Aspartylglucosaminuria (AGU) is a rare genetic disorder that affects development, cognition and multiple body systems. Symptoms appear in early childhood and progressively worsen with age.2-4
Signs and symptoms, according to age, may include:
Infancy to early childhood (birth to 6 years)
Childhood to adolescence (7-18 years)
Adulthood (18+ years)
AGU is a progressive disorder with worsening symptoms over time. Life expectancy extends into middle adulthood with proper medical care but affected people require lifelong support due to increasing physical and cognitive impairments.
Aspartylglucosaminuria (AGU) is caused by disease causing changes (pathogenic variants) in the AGA gene.
The AGA gene has instructions to make (codify) an enzyme called aspartylglucosaminidase. This enzyme is active in lysosomes which are structures inside cells that act as recycling centers. Within lysosomes, the enzyme helps break down complex chains of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). Variants in the AGA gene can lead to a shortage of aspartylglucosaminidase in lysosomes. Without enough of this enzyme, glycoproteins cannot be broken down properly and start to build up inside the lysosomes. This buildup disrupts normal cell function and can lead to cell death. Nerve cells in the brain are especially affected, and losing these cells causes many of the symptoms of aspartylglucosaminuria.4-6
Inheritance
Aspartylglucosaminuria is inherited in an autosomal recessive manner.
Recessive genetic disorders occur when an individual inherits a disease-causing gene variant from each parent. If an individual receives one normal gene and one disease-causing gene variant, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the gene variant and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.4
Aspartylglucosaminuria (AGU) is most common in individuals of Finnish descent but has been reported worldwide. In Finland, about 260 people have been reported in the medical literature with AGU and 160 of them are still alive. The condition affects 1 in 3,643 children in eastern Finland. Each year, 1 to 3 children with AGU are born in Finland, resulting in about 1.7 to 5 cases for every 100,000 babies born. Globally, there are around 200 to 300 people living with AGU with about 30 in Sweden and Norway. Most Finnish patients (98%) have AGU due to a specific variant of the AGA gene and about 1 in 50 to 60 Finns carry this gene variant.3,4
Doctors may suspect AGU in individuals who show a combination of the following signs and symptoms: 3,4
Laboratory tests may include: 3,4
Imaging tests can include: 3,4
In addition, a family history of AGU may suggest a risk, but not having a family history does not mean a person cannot have AGU.
Genetic testing identifying variants in the AGA gene can confirm the diagnosis. Tests can also be done on amniotic fluid or tissue samples from the placenta to check for AGU before a baby is born.3,4
Recent studies using advanced imaging techniques have shown changes in how the brain connects in people with AGU. Machine learning methods using MRI data have also been successful in distinguishing people with AGU from healthy people with a low error rate.6
Affected people may need to be seen by a team of medical specialists who should work together in a coordinated manner. The team should include neurologists, orthopedists, physical therapists and other healthcare providers.
Regular checkups help track development, manage symptoms and adjust treatments. This includes: 4,5
Common issues such as seizures, mood swings, ear infections and arthritis are typically treated according to standard medical guidelines. For instance, carbamazepine is frequently prescribed to control seizures.
Behavioral and sleep problems are addressed through behavioral therapy and when necessary, medication. Adults may benefit from therapies like physiotherapy and music therapy.
Ear, nose and throat (ENT) specialists might recommend procedures such as ear tube placement, tonsil removal, or adenoid removal for ear infections.
Bone and joint issues should be monitored and treated by orthopedists who may suggest physical therapy, joint care and osteoporosis management.
Additionally, families can find support through support groups, respite care and social work assistance. Care coordination is essential for managing multiple medical appointments, medications and equipment. 4-6
Since AGU affects the brain, effective treatments must be able to cross the blood-brain barrier, which typically prevents most medications from reaching the brain. Researchers are currently studying enzyme replacement therapies (ERTs) as a possible treatment for AGU.7
Another option, hematopoietic stem cell transplantation, may improve health, especially if done before serious brain issues develop. However, the results can be unpredictable. More research is necessary, including larger studies and exploring newborn screening, to improve early diagnosis and find better treatment options for AGU.8
The study MT2013-31 Allo HCT for Metabolic Disorders and Severe Osteopetrosis is examining allogeneic hematopoietic cell transplantation (HCT) for patients with metabolic disorders and severe osteopetrosis.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/