congenital disorder of glycosylation Ir

Congenital Disorders of Glycosylation (CDG): A Rare Genetic Condition

Congenital disorders of glycosylation (CDG) is a group of rare genetic disorders that affect the body's ability to attach sugars to proteins and fats [4]. This condition is caused by defects in various steps along the glycan synthesis pathway, leading to over 130 different diseases [2][7].

Symptoms and Characteristics

Individuals with CDG may experience a range of symptoms, including:

• Developmental delays
• Imbalance
• Muscle weakness
• Nerve damage
• Vision issues
• Gastrointestinal problems
• Poor growth
• Liver disease [3]

Some individuals with CDG may also have distinctive facial features, such as a high forehead, triangular face, large ears, and thin upper lip [5].

Types of CDG

CDG is a genetically and clinically heterogeneous group of diseases, meaning that each type can present differently in different individuals. Some types of CDG include:

• SRD5A3-congenital disorder of glycosylation (SRD5A3-CDG), which primarily causes neurological and vision problems [9]
• Other types of CDG may cause a range of symptoms, including those listed above

References

[1] IJ Chang. Congenital disorders of glycosylation: A rapidly expanding group of rare genetic diseases. (2018)

[2] DM Krasnewich. Congenital disorders of glycosylation (CDGs): A review of the literature. (Cited by 2)

[3] Jun 12, 2024 - Developmental delays and other symptoms associated with CDG

[4] Congenital disorders of glycosylation (CDG) is a group of rare genetic disorders that affect how sugars attach to proteins and fats in the body.

[5] Distinctive facial features are sometimes present in affected individuals, including a high forehead, triangular face, large ears, and thin upper lip.

[6] IJ Chang. Congenital disorders of glycosylation: A rapidly expanding group of rare genetic diseases. (2018)

[7] IJ Chang. Congenital disorders of glycosylation are a genetically and clinically heterogeneous group of >130 diseases caused by defects in various steps along glycan synthesis pathway.

[8] DJ Lefeber. Inherited human diseases that are caused by defects in glycan biosynthesis and metabolism (congenital disorders of glycosylation, CDGs). (2022)

[9] SRD5A3-congenital disorder of glycosylation (SRD5A3-CDG) is an inherited condition that primarily causes neurological and vision problems.

Symptoms of Congenital Disorder of Glycosylation (CDG)

CDG can manifest a wide range of symptoms, varying in severity from mild to severe, disabling or life-threatening. The following are some common signs and symptoms associated with CDG:

• Developmental delays: Individuals with CDG may experience delayed development, including speech, language, and motor skills [2].
• Muscle weakness and floppiness (hypotonia): Muscle tone can be affected, leading to a range of symptoms from mild weakness to severe muscle floppiness [3].
• Liver disease: Liver problems are common in individuals with CDG, including liver dysfunction and cirrhosis [4].
• Abnormal bleeding or blood clotting: Some people with CDG may experience issues with blood clotting, leading to abnormal bleeding [3].
• Crossed or misaligned eyes (strabismus): Eye movement problems can occur in individuals with CDG, resulting in crossed or misaligned eyes [7].
• Vision issues: Vision problems are a common symptom of CDG, including blurred vision and other eye-related issues [2].
• Gastrointestinal problems: Individuals with CDG may experience vomiting, diarrhea, and other gastrointestinal issues [7].
• Poor growth: Poor growth and development can be a sign of CDG, particularly in infants and young children [2].

Age-specific symptoms

Symptoms can vary depending on the age of the individual:

• Infants and young children: Developmental delays, muscle weakness, liver disease, and gastrointestinal problems are common symptoms in this age group.
• Adolescents and adults: Individuals with PMM2-CDG may experience reduced sensation and weakness in their arms and legs (peripheral neuropathy) during adolescence or adulthood [4].
• Older individuals: Adults with PMM2-CDG can live until their 7th or 8th decades, experiencing stable cognitive delay, peripheral neuropathy, and progressive thoracic and spinal problems [6].

It's essential to note that each individual may experience a unique set of symptoms, and the severity of CDG can vary widely. If you suspect someone has CDG, it's crucial to consult with a medical professional for proper diagnosis and treatment.

References:

[1] Not provided (CDG description) [2] 2. Jun 12, 2024 [3] 3. What are the symptoms of CDG? [4] 4. During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal ... [5] Not provided (PMM2-CDG description) [6] by IJ Chang · 2018 · Cited by 247 — Adults with PMM2-CDG may live until their 7th or 8th decades with stable cognitive delay, peripheral neuropathy, and progressive thoracic and spinal ... [7] Jun 7, 2023 — CDG Symptoms · Abnormal fat distribution · Bleeding or blood clotting issues · Vomiting and diarrhea · Crossed eyes (strabismus) · Distinctive facial ...

Diagnostic Tests for Congenital Disorder of Glycosylation (CDG)

Congenital disorders of glycosylation (CDG) are a group of rare genetic disorders that affect the addition of sugar building blocks, called glycans, to proteins in cells throughout the body. Diagnostic tests play a crucial role in identifying CDG and guiding treatment.

Recommended First-Tier Test

The recommended first-tier test to screen for congenital disorders of glycosylation (CDG) is a biochemical test that analyzes transferrin and apolipoprotein [9][10]. This test is often considered the standard first-screen test for N-linked protein glycosylation disorders [5].

Isoelectric Focusing/Polyacrylamide Gel Electrophoresis (IEF)

Still common screening tests for most CDG types, including CDG Ia, are isoelectric focusing/polyacrylamide gel electrophoresis (IEF) [1]. IEF demonstrates the abnormal glycosylation pattern of transferrin.

Serum Transferrin Isoelectrofocusing

Analysis via serum transferrin isoelectrofocusing is often considered the standard first-screen test for N-linked protein glycosylation disorders; however, it may not be sufficient to confirm a diagnosis [5].

Genetic Testing

Molecular testing, usually with next-generation sequencing methods, is necessary to establish a genetic diagnosis in CDG. This type of testing can identify specific genetic mutations associated with the disorder [14][6].

Other Diagnostic Tests

In addition to biochemical and genetic tests, other diagnostic tests may be used to help diagnose CDG, such as liver function tests, coagulation studies, and blood glucose measurements [12].

References:

[1] Marklová E. (2007) - Still common screening test for most CDG types, including CDG Ia, is isoelectric focusing/polyacrylamide gel electrophoresis (IEF).

[5] Analysis via serum transferrin isoelectrofocusing is often considered the standard first-screen test for N-linked protein glycosylation disorders; however, it may not be sufficient to confirm a diagnosis.

[9] The recommended first-tier test to screen for congenital disorders of glycosylation (CDG) is a biochemical test that analyzes transferrin and apolipoprotein.

[10

Treatment Options for Congenital Disorders of Glycosylation (CDG)

Congenital disorders of glycosylation (CDG) are a group of rare genetic disorders that affect the body's ability to synthesize glycans, which are essential for various cellular processes. While there is no cure for CDG, several treatment options have been explored and implemented to manage the symptoms and improve the quality of life for affected individuals.

Nutritional Therapies

• Oral galactose supplementation has been shown to be effective in treating SLC35A2-CDG, where it increases UDP-galactose supplies and improves glycosylation [1].
• Oral mannose supplementation therapy is another nutritional approach that has successfully restored glycosylation in patients with PMM2-CDG [7].

Other Therapeutic Approaches

• Gene therapy has been explored as a potential treatment for CDG, although it is still in the early stages of development [6].
• Activated sugars and transplantation have also been investigated as possible therapeutic options for CDG [6].

Managing Seizures in CDG

• Seizures are a common symptom in some forms of CDG. Doctors in epilepsy programs may have access to various medications, including new options being studied in clinical trials [8].
• However, it's essential to note that there is still no cure for CDG, and treatment outcomes can vary depending on the specific type of CDG and individual patient factors [9].

Current Research and Development

• Researchers are actively exploring new therapeutic approaches for CDG, including gene therapy and nutritional interventions.
• Ongoing studies aim to improve our understanding of CDG and develop more effective treatments for affected individuals.

References:

[1] Park JH (2021) - [1] [7] Monticelli M (2023) - [7] [6] Verheijen J (2020) - [6] [8] Epilepsy Program (no specific reference) [9] Brasil S (2022) - [9]

Note: The numbers in square brackets refer to the corresponding search results provided in the context.

Differential Diagnosis of Congenital Disorder of Glycosylation (CDG)

Congenital disorders of glycosylation (CDGs) are a group of rare genetic disorders caused by mutations in genes involved in protein and lipid glycosylation. When considering the differential diagnosis of CDG, several conditions should be taken into account.

• Hypoglycemia: Unexplained hypoglycemia can be a symptom of CDG Ib, which should be considered in the differential diagnosis [10].
• Chronic Diarrhea: Chronic diarrhea is another symptom that may indicate CDG, particularly CDG Ib [10].
• Liver Disease: Liver disease, including liver dysfunction and cirrhosis, can be associated with CDG [9].
• Coagulopathy: Coagulopathy, or bleeding disorders, can also be a manifestation of CDG [10].

Other conditions that may present similarly to CDG include:

• Carbohydrate-deficient glycoprotein syndrome (CDGS): This is an older term for CDG and should not be confused with the current classification.
• PMM2-CDG: A subtype of CDG characterized by mutations in the PMM2 gene, which can present with similar symptoms to other forms of CDG.

It's essential to consider these conditions as part of the differential diagnosis when evaluating patients suspected of having a congenital disorder of glycosylation.