Aspartylglucosaminuria
Disease Details
Family Health Simplified
- Description
- Aspartylglucosaminuria is a rare inherited metabolic disorder characterized by a deficiency in the enzyme aspartylglucosaminidase, leading to the accumulation of glycoasparagines in tissues, which results in progressive intellectual disability and various physical symptoms.
- Type
- Aspartylglucosaminuria is an autosomal recessive disorder.
- Signs And Symptoms
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At birth, there is no sign that a child will develop symptoms of aspartylglucosaminuria. Typically, signs and symptoms become apparent between two and four years of age and become progressively worse as the individual ages. The following signs and symptoms may appear:
Individuals are more prone to respiratory infections
Development of scoliosis
Seizures or difficulty with movement
Skin and joints may become loose
Facial features change progressively; this may include:thickening of the skin
features becoming more prominent
large head
broad lower jaw
short, broad nose
rounded cheeksProgression of developmental and mental disabilities, including:progressive loss of speech
decrease in mental functioning
before school age, concentration lowers
development continues, but becomes slower than usualAn intellectual peak occurs in the mid-teens and allows a plateau for the disease. Once an individual hits the age of 25–30 the decrease begins again, including:learned skills become lost which result in severe learning disabilities
motor skills deteriorate
individuals become less mobile and more dependent(Children are physically uncoordinated, but remain able to play sports and do everyday activities until they reach adulthood.)
During the first year of life inguinal and umbilical hernias are common.
Less severe symptoms include:enlargement of the spleen and liver
diarrheaPeople with aspartylglucosaminuria may have lower than average height, because they tend to go through puberty earlier.
Epilepsy may develop in adulthood.
Finnish studies have shown that life expectancy is shorter than average. - Prognosis
- Individuals with AGU typically have normal development in infancy. Around the age of 2–4 years, they begin showing signs of developmental delay, but development is still progressing. Initial symptoms may present as clumsiness and/or speech delay. Individuals with AGU also show increased upper respiratory infections. Development continues until about puberty; however, an individual at 13–16 years of age typically shows mental and motor development similar to a 5-6 year old. Around puberty, a gradual decline in mental abilities and motor skills occurs. This progressive decline continues until about age 25–28, when rapid impairment of abilities occurs, resulting in severe intellectual disability.
- Onset
- Aspartylglucosaminuria (AGU) typically presents in early childhood, around the age of 2 to 4 years. Initial symptoms might include developmental delays and mild intellectual disability, which progressively worsen with age.
- Prevalence
- Aspartylglucosaminuria is an extremely rare genetic disorder. Its prevalence is notably higher in Finland, where it affects approximately 1 in 18,000 individuals. Outside of Finland, the prevalence is significantly lower and not well-defined due to its rarity.
- Epidemiology
- Aspartylglucosaminuria is estimated to affect 1 in 18,500 people in Finland. This condition is less common in other countries, but the incidence is unknown. Even though this disease can occur in various races and ethnicities, another study backed this finding up by stating that 1 in 26,000 people in Finland had the disease and that 1 in 18,000 were carriers.After trisomy 21 and fragile X syndrome, this is the most frequent multiple congenital anomaly/intellectual disability syndrome in Finland.
- Intractability
- Aspartylglucosaminuria is considered an intractable disease. It is a rare, inherited lysosomal storage disorder characterized by progressive intellectual disability and physical deterioration. Current treatments focus on managing symptoms and improving quality of life, as no cure is available.
- Disease Severity
- Aspartylglucosaminuria is classified as a severe, progressive lysosomal storage disorder. It typically becomes apparent in early childhood with developmental delays and continues to progress with worsening intellectual disability and physical symptoms.
- Healthcare Professionals
- Disease Ontology ID - DOID:0050461
- Pathophysiology
- Aspartylglucosaminuria is a rare lysosomal storage disorder caused by a deficiency in the enzyme aspartylglucosaminidase. This enzyme is crucial for the breakdown of glycoproteins, specifically the aspartylglucosamine linkage. When this enzyme is deficient, glycoasparagines accumulate in the lysosomes of various tissues, including the brain, leading to progressive cellular and tissue damage. Over time, this accumulation results in developmental delays, intellectual disability, skeletal abnormalities, and other systemic issues.
- Carrier Status
- Aspartylglucosaminuria is an autosomal recessive lysosomal storage disorder. Carrier status for autosomal recessive conditions like aspartylglucosaminuria means that an individual has one mutated copy of the AGA gene but does not typically show symptoms of the disease. Carriers can pass the mutated gene to their offspring. If both parents are carriers, there is a 25% (1 in 4) chance with each pregnancy of having a child affected by aspartylglucosaminuria.
- Mechanism
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Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by mutations in the AGA gene. This gene encodes the enzyme aspartylglucosaminidase, which is essential for the normal breakdown of glycoproteins in lysosomes.
**Mechanism:**
In AGU, mutations in the AGA gene lead to a deficiency or malfunction of the aspartylglucosaminidase enzyme. This results in the accumulation of glycoasparagine and other glycoasparaginyl compounds in various tissues, which disrupts normal cellular function and leads to the symptoms associated with the disorder.
**Molecular Mechanisms:**
1. **Gene Mutation:** Mutations in the AGA gene lead to either complete loss of enzyme activity or production of a dysfunctional enzyme.
2. **Enzyme Deficiency:** The lack of functional aspartylglucosaminidase impairs the breakdown of glycoasparagine in the lysosomes.
3. **Substrate Accumulation:** Undegraded glycoasparagine accumulates within the lysosomes, which impairs cellular processes and contributes to the clinical manifestations of AGU.
4. **Cellular Dysfunction:** The buildup of glycoasparagine disrupts lysosomal function, leading to cellular dysfunction and resulting in various physical and neurological symptoms.
Overall, the molecular mechanisms underlying AGU involve the disruption of normal lysosomal degradation pathways due to enzymatic deficiencies, leading to the accumulation of harmful substrates within cells. - Treatment
- No treatment is available to cure or slow down the progression of aspartylglucosaminuria. Bone marrow transplants have been conducted in hope that the bone marrow will produce the missing enzyme. The results of the tests thus far have shown to be inconclusive.
- Compassionate Use Treatment
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Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder that typically lacks definitive treatment options. Here are some approaches related to compassionate use, off-label, or experimental treatments:
1. **Enzyme Replacement Therapy (ERT):** Experimental studies have investigated the use of recombinant human aspartylglucosaminidase but, as of now, it is not an established treatment available for routine use.
2. **Gene Therapy:** Preclinical studies and early-phase clinical trials are exploring gene therapy as a potential treatment for AGU. This approach aims to correct the underlying genetic defect responsible for the disease.
3. **Substrate Reduction Therapy (SRT):** While primarily used in other lysosomal storage disorders, experimental research is ongoing to assess the efficacy of SRT in managing AGU symptoms by reducing the accumulation of substrate that causes cell damage.
4. **Bone Marrow Transplantation (BMT):** Although not a standard treatment for AGU, bone marrow or stem cell transplantation has been considered in severe cases and in the context of clinical trials or compassionate use programs.
It's important for patients to discuss available treatment options, including participation in clinical trials and access to experimental therapies, with their healthcare providers. - Lifestyle Recommendations
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Aspartylglucosaminuria (AGU) is a rare inherited lysosomal storage disorder. While there are no specific lifestyle recommendations that can cure or halt the progression of AGU, supportive care and management strategies can improve the quality of life for those affected. Here are some general lifestyle recommendations:
1. **Regular Medical Follow-Up**: Regular appointments with a healthcare team that may include geneticists, neurologists, and other specialists to monitor the progression and address complications.
2. **Physical Therapy**: Engaging in physical therapy to help maintain mobility, muscle strength, and coordination.
3. **Occupational Therapy**: Occupational therapy can assist with daily living activities and improve independence.
4. **Speech Therapy**: Speech therapy can help enhance communication skills, which may be affected by AGU.
5. **Healthy Diet**: Ensure a balanced and nutritious diet to support overall health and well-being. This includes monitoring for potential issues like swallowing difficulties and adjusting food consistency as needed.
6. **Regular Exercise**: Encourage regular, gentle exercise tailored to the individual's abilities to maintain physical fitness and overall health.
7. **Mental Health Support**: Psychological support or counseling for individuals and families to cope with the emotional and social challenges of the condition.
8. **Education and Social Support**: Engage with support groups, special education programs, and social services that can provide additional resources and community support.
It's important to work closely with healthcare providers to tailor these recommendations to the individual's specific needs. - Medication
- Aspartylglucosaminuria is a rare genetic disorder characterized by the accumulation of glycoasparagine due to the deficiency of the enzyme aspartylglucosaminidase. Currently, there is no specific medication approved to treat aspartylglucosaminuria. Management primarily focuses on symptomatic treatment and supportive care, including physical therapy, special education, and management of complications as they arise. Regular monitoring by a multidisciplinary medical team is often required to address the various health issues associated with the condition.
- Repurposable Drugs
- As of now, there are no well-established repurposable drugs for the treatment of aspartylglucosaminuria (AGU). This rare genetic lysosomal storage disorder currently lacks specific therapies that have been widely accepted or identified through drug repurposing efforts. Treatment mainly focuses on managing symptoms and supportive care. Researchers are actively investigating potential therapeutic approaches, and ongoing clinical trials may provide new insights into repurposable drugs in the future.
- Metabolites
- Aspartylglucosaminuria is a lysosomal storage disorder characterized by the accumulation of glycoasparagine due to a deficiency in the enzyme aspartylglucosaminidase. This condition leads to the progressive storage of these unmetabolized glycoprotein degradation products within the lysosomes of various tissues.
- Nutraceuticals
- Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder caused by a deficiency in the enzyme aspartylglucosaminidase. There is limited evidence on the effectiveness of nutraceuticals in treating AGU. Current treatment primarily focuses on managing symptoms and supportive care. Research into enzyme replacement therapy and other treatments is ongoing.
- Peptides
- Aspartylglucosaminuria is a rare lysosomal storage disorder caused by a deficiency in the enzyme aspartylglucosaminidase. This deficiency leads to the accumulation of glycoasparagine and related glycopeptides in the lysosomes. Nan, or nanoparticles, are not typically related to the standard understanding or treatment of this condition.