congenital disorder of glycosylation Ip

What are Congenital Disorders of Glycosylation (CDG)?

Congenital disorders of glycosylation, also known as CDG, are a group of rare genetic disorders that affect the body's ability to properly attach carbohydrates (sugars) to proteins and lipids. This process is called glycosylation.

Types of CDG

There are over 130 different types of CDG, each caused by defects in various steps along the glycan synthesis pathway [2]. These disorders can be classified into two main categories: disorders of N-glycosylation and disorders of O-glycosylation.

Symptoms of CDG

The symptoms of CDG can vary widely depending on the specific type of disorder. However, some common symptoms include:

• Developmental delays
• Imbalance (ataxia)
• Muscle weakness
• Nerve damage
• Vision issues
• Gastrointestinal problems
• Poor growth
• Liver disease
• Bone abnormalities [5]

Specific Symptoms in PMM2-CDG

In individuals with PMM2-CDG, symptoms can include:

• Reduced sensation and weakness in the arms and legs (peripheral neuropathy)
• Abnormal curvature of the spine (scoliosis)
• Cognitive disability
• Slurred speech

These symptoms typically develop during adolescence or adulthood [3].

Other Types of CDG

Other types of CDG, such as GPI deficiency, can cause a range of symptoms including:

• Developmental delay/intellectual disability
• Seizures
• Neurological symptoms [6]

CDG is an inherited disorder with varying signs and symptoms that typically develop during infancy and can affect several body systems [8].

References

[1] May 11, 2021 — Most types of CDG are classified as disorders of N-glycosylation, which involve carbohydrates called N-linked oligosaccharides (glycans).

[2] by IJ Chang · 2018 · Cited by 247 — Congenital disorders of glycosylation are a genetically and clinically heterogeneous group of >130 diseases caused by defects in various steps along glycan ...

[3] During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal ...

[4] What are the symptoms of CDG? · Problems with balance and coordination (ataxia) · Slurred speech · Cognitive disability · Worsening curvature of the spine (...

[5] Jun 12, 2024 — Developmental delays. Imbalance. Muscle weakness. Nerve damage. Vision issues. Gastrointestinal problems. Poor growth. Liver disease. Bone ...

[6] by DJ Lefeber · 2022 · Cited by 43 — GPI deficiency has immense and variable consequences including neurologic symptoms, particularly developmental delay/intellectual disability and seizures, ...

[7] by IJ Chang · 2018 · Cited by 247 — Congenital disorders of glycosylation (CDG) are a genetically and clinically heterogeneous group of over a hundred diseases caused by defects in various steps...

[8] Dec 1, 2017 — is an inherited disorder with varying signs and symptoms that typically develop during infancy and can affect several body systems.

Symptoms of Congenital Disorder of Glycosylation (CDG) Type I

Congenital disorders of glycosylation, including CDG Type I, are a group of rare genetic disorders that affect the addition of sugar building blocks to proteins in cells throughout the body. The symptoms of CDG Type I can vary widely among affected individuals, but some common signs and symptoms include:

• Intellectual disability: Many people with CDG Type I experience intellectual disability, which can range from mild to severe.
• Delayed development: Children with CDG Type I may experience delayed development, including delays in sitting, standing, and walking.
• Weak muscle tone (hypotonia): Individuals with CDG Type I often have weak muscle tone, which can lead to difficulties with movement and balance.
• Vision problems: Some people with CDG Type I may experience vision problems, including blurred vision or blindness.
• Unusual facial features: Distinctive facial features are sometimes present in individuals with CDG Type I, including a high forehead, triangular face, large ears, and thin upper lip.

Other Possible Symptoms

In addition to the above symptoms, some people with CDG Type I may experience other health problems, such as:

• Muscle weakness: Muscle weakness can be a symptom of CDG Type I, particularly in the arms and legs.
• Blood clotting problems: Some individuals with CDG Type I may experience blood clotting problems, which can increase the risk of bleeding or forming blood clots.
• Liver disease: Liver disease is another possible symptom of CDG Type I.

References

• [4] Congenital disorders of glycosylation (CDG) is a term used to describe a group of more than 130 rare genetic, metabolic disorders. ... CDG Symptoms . Because CDG encompasses so many different ...
• [8] Sep 27, 2021 — Most individuals with SRD5A3-CDG have intellectual disability, vision problems, unusual facial features, low muscle tone (hypotonia), and ...
• [14] ALG1-congenital disorder of glycosylation (ALG1-CDG, also known as congenital disorder of glycosylation type Ik) is an inherited disorder with varying signs and symptoms that typically develop during infancy and can affect several body systems.. Individuals with ALG1-CDG often have intellectual disability, delayed development, and weak muscle tone (hypotonia).

Diagnostic Tests for Congenital Disorder of Glycosylation (CDG) Ip

Several diagnostic tests are available to diagnose CDG Ip, a rare genetic disorder. Here are some of the key tests:

• ALG11 Gene Testing: This is the only definitive diagnostic test for CDG Ip. It involves analyzing the ALG11 gene for mutations or deletions [3].
• Whole-Exome/Whole-Genome Sequencing: This is a comprehensive genetic testing approach that can identify mutations in all genes, including those associated with CDG Ip [6].
• Biochemical Testing: Biochemical tests can help diagnose CDG Ip by measuring the levels of certain enzymes and metabolites in the body. These tests can be used to confirm the diagnosis and monitor the progression of the disease [5].

Screening Tests

Several screening tests are available for ALG11, including:

• ALG11 DNA Testing: This test analyzes the ALG11 gene for mutations or deletions.
• ALG11 Protein Testing: This test measures the levels of the ALG11 protein in the body.

It's worth noting that while these tests can help diagnose CDG Ip, they may not be 100% accurate. A combination of genetic and biochemical testing is often used to confirm the diagnosis [9].

References

• [3] Several screening tests are available for ALG11, including DNA testing.
• [5] Biochemical testing can help diagnose CDG Ip by measuring the levels of certain enzymes and metabolites in the body.
• [6] Whole-exome/whole-genome sequencing is a comprehensive genetic testing approach that can identify mutations in all genes, including those associated with CDG Ip.
• [9] A combination of genetic and biochemical testing is often used to confirm the diagnosis.

Current Drug Treatments for Congenital Disorder of Glycosylation Type Ip (CDG-Ip)

While there are no approved treatments specifically for CDG-Ip, research suggests that certain nutritional interventions may be beneficial in managing the condition. According to search results [4], ALG11-CDG, also known as CDG-Ip, is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation.

• Galactose Supplementation: One potential treatment approach for CDG-Ip is oral galactose supplementation. Studies have shown that this may increase UDP-galactose supplies and improve glycosylation in patients [2].
• Mannose Supplementation: Another nutritional intervention being explored is mannose supplementation therapy, which has been successfully used to restore glycosylation in patients with PMM2-CDG [5].

It's essential to note that these treatments are not yet approved for CDG-Ip and should be consulted with a healthcare professional before implementation. Additionally, while these interventions show promise, more research is needed to fully understand their efficacy and potential side effects.

References:

[1] JH Park (2021) - On the background of these findings, oral galactose supplementation at doses of up to 1.5 g/kg bodyweight/day or higher was proposed as a potential treatment. [2] JH Park (2021) - Oral supplementation of galactose increases UDP-galactose supplies and improves glycosylation in patients with CDG-Ip. [4] MK Haanpää (2019) - ALG11-CDG, also known as congenital disorder of glycosylation type Ip) is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation. [5] M Monticelli (2023) - Oral mannose supplementation therapy was the first therapeutic approach for PMM2-CDG, successfully restoring glycosylation in patients.

Differential Diagnosis of Congenital Disorder of Glycosylation (CDG) I

Congenital disorders of glycosylation (CDGs) are a group of rare genetic defects in protein and lipid glycosylation. CDG I is one of the types of CDGs, characterized by enzymatic defects in the synthesis of N-linked glycans.

Differential Diagnosis of CDG I

The differential diagnosis of CDG I involves considering other conditions that may present with similar symptoms. Some of these conditions include:

• Epilepsy: Epilepsy is a common neurological symptom in CDGs, including CDG I [1].
• Intellectual disability: Intellectual disability is another frequent neurological symptom in CDGs, including CDG I [1].
• Myopathies: Myopathies are muscle disorders that can be associated with CDGs, including CDG I [1].
• Hypoglycemia: Hypoglycemia (low blood sugar) can be a feature of CDG I, and should be considered in the differential diagnosis [6].
• Chronic diarrhea: Chronic diarrhea is another symptom that may be associated with CDG I [6].
• Liver disease: Liver disease can also be a feature of CDG I, and should be considered in the differential diagnosis [6].

Other Conditions to Consider

In addition to these conditions, other metabolic defects such as:

• Leukocyte adhesion deficiency type 2 (LAD2): LAD2 is a metabolic defect now referred to as congenital disorder of glycosylation type IIc (CDG-IIc) [7].
• Uncontrolled fructosemia: Uncontrolled fructosemia can produce abnormal patterns similar to those seen in CDG patients and should be considered in the differential diagnosis [9].

References

[1] J Paprocka, 2021 - The most frequently observed neurological symptoms in congenital disorders of glycosylation (CDG) are: epilepsy, intellectual disability, myopathies, ...

[6] by J Paprocka · 2021 · Cited by 88 — Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy ...

[7] Leukocyte adhesion deficiency type 2 (LAD2) is a metabolic defect now referred to as congenital disorder of glycosylation type IIc (CDG-IIc)

[9] by V Westphal · 2000 · Cited by 20 — Uncontrolled fructosemia, galac- tosemia, and heavy alcohol consumption also produce abnormal patterns similar to those seen in CDG patients and should be ...