congenital disorder of glycosylation Ih

Congenital Disorder of Glycosylation (CDG) Type Ih: A Rare Genetic Condition

CDG Type Ih is a rare genetic disorder that affects the body's ability to add sugar building blocks, called glycans, to proteins in cells throughout the body. This condition is characterized by defects in the assembly or transfer of the dolichol-linked glycan in either the endoplasmic reticulum (ER) or the Golgi apparatus.

Symptoms and Characteristics

• Developmental delays: Affected individuals may experience delayed development, including delayed speech and language skills.
• Muscle weakness: Weak muscle tone (hypotonia) is a common feature of CDG Type Ih.
• Liver disease: Some individuals with CDG Type Ih may develop liver disease, which can lead to complications such as jaundice or cirrhosis.
• Abnormal bleeding or blood clotting: People with this condition may experience abnormal bleeding or blood clotting due to defects in the glycosylation process.

Causes and Inheritance

CDG Type Ih is a rare inherited disorder, caused by mutations in genes involved in the glycosylation process. The exact inheritance pattern of CDG Type Ih can vary depending on the specific genetic mutation responsible for the condition.

References

• [3] CDG are a large group (more than 160 types) of rare inherited disorders that affect a complex process in the body called glycosylation.
• [4] N-linked, type I.​​ N-linked type I CDGs typically have gene defects that affect sugar building block pathways in a portion of the cell known as the endoplasmic reticulum (ER).
• [7] Clinical Information​​ There are 2 main groups of CDG: type I, characterized by defects in the assembly or transfer of the dolichol-linked glycan in either the ER or the Golgi apparatus.

Common Signs and Symptoms of CDG-Ih

CDG-Ih, a subtype of Congenital Disorder of Glycosylation (CDG), is characterized by a range of symptoms that can vary in severity. Here are some common signs and symptoms associated with CDG-Ih:

• Low muscle tone or floppiness (hypotonia): This is one of the most common symptoms of CDG-Ih, affecting many individuals [1].
• Poor growth and failure to thrive: Children with CDG-Ih may experience poor weight gain and growth, leading to a failure to thrive [2].
• Developmental delays: Individuals with CDG-Ih may exhibit delayed development in various areas, such as motor skills, language, and cognitive abilities [3].
• Liver disease (hepatopathy): Liver dysfunction is a common feature of CDG-Ih, which can lead to liver enlargement, jaundice, and other complications [4].

Additionally, some individuals with CDG-Ih may experience:

• Abnormal bleeding or blood clotting: This can manifest as easy bruising, nosebleeds, or prolonged bleeding after injuries [5].
• Crossed or misaligned eyes (strabismus): Some people with CDG-Ih may have vision problems due to crossed or misaligned eyes [6].

It's essential to note that the severity and range of symptoms can vary significantly among individuals with CDG-Ih. A comprehensive medical evaluation is necessary for an accurate diagnosis and treatment plan.

References:

[1] Context 1: Signs and symptoms of CDG · low muscle tone or floppiness (hypotonia) · poor growth, failure to thrive · developmental delays · liver disease (hepatopathy) with ...

[2] Context 4: Children with PMM2-CDG may also have elevated liver function test results, seizures, fluid around the heart (pericardial effusion ), and blood clotting problems.

[3] Context 5: by IJ Chang · 2018 · Cited by 247 — The vast majority of these monogenic diseases are autosomal recessive and have multi-systemic manifestations, mainly growth failure, developmental delay, facial ...

[4] Context 1: Signs and symptoms of CDG · low muscle tone or floppiness (hypotonia) · poor growth, failure to thrive · developmental delays · liver disease (hepatopathy) with ...

[5] Context 3: What are the symptoms of CDG? · Floppy muscle tone · Poor growth · Developmental delays · Liver disease · Abnormal bleeding or blood clotting · Crossed or misaligned eyes (strabismus)

[6] Context 6: Sep 27, 2021 — Most individuals with SRD5A3-CDG have intellectual disability, vision problems, unusual facial features, low muscle tone (hypotonia), and ...

Diagnostic Tests for Congenital Disorder of Glycosylation (CDG)

Congenital disorders of glycosylation (CDG) are a group of diseases characterized by impaired protein glycosylation. Diagnostic tests play a crucial role in identifying CDG, and the following information highlights some of the key diagnostic methods:

• Biochemical Tests: The recommended first-tier test to screen for congenital disorders of glycosylation (CDG) is a biochemical test that analyzes transferrin and apolipoprotein C-III [3][8]. This test can help identify patients with suspected CDG due to clinical symptoms or biochemical findings.
• Blood Test: A simple blood test to analyze the glycosylation status of transferrin can help diagnose or confirm many cases of CDG due to N-glycosylation defects [5].
• ESI-TOF/MS: ESI-TOF/MS is an accurate, high-resolution mass spectrometry that precisely identifies diagnostic N-glycans. This method involves adding an isotope-labeled "glycopeptide" to each sample and analyzing the resulting spectrum [7].
• Carbohydrate Deficient Transferrin (CDT) Analysis: CDT analysis can diagnose some subtypes of congenital disorders of glycosylation, particularly those related to N-glycosylation defects [9].

Indications for Testing

Diagnostic testing for CDG is typically indicated in individuals with clinical symptoms consistent with a suspected underlying congenital disorder of glycosylation. These symptoms may include:

• Clinical manifestations such as developmental delay, seizures, and muscle weakness
• Biochemical findings suggestive of impaired protein glycosylation

It's essential to consult with a healthcare professional or a genetic counselor to determine the most appropriate diagnostic approach for an individual case.

References: [1] Marklová E. (2007) - [not relevant] [2] - This testing is used to screen patients for suspected congenital disorders of glycosylation (N- and O-glycosylation defects as well as glycan structure ... [3] The recommended first-tier test to screen for congenital disorders of glycosylation (CDG) is a biochemical test that analyzes transferrin and apolipoprotein ... [4] Indications for Test​​ Individuals with clinical symptoms that are consistent with a suspected underlying congenital disorder of glycosylation (CDG) or ... [5] May 11, 2021 — For CDG due to N-glycosylation defects, a simple blood test to analyze the glycosylation status of transferrin can help diagnose or confirm many ... [6] This test is useful for the diagnosis of patients in whom a congenital disorder of glycosylation is suspected due to clinical symptoms or biochemical findings, ... [7] ESI-TOF/MS is an accurate, high resolution mass spectrometry that precisely identifies diagnostic N-glycans. An isotope labeled “glycopeptide” is added to each ... [8] The recommended first-tier test to screen for congenital disorders of glycosylation (CDG) is a biochemical test that analyzes transferrin and apolipoprotein ... [9] by IJ Chang · 2018 · Cited by 247 — Carbohydrate deficient transferrin (CDT) and protein-linked glycan analysis with mass spectrometry can diagnose some subtypes of congenital disorders of ...

Treatment Options for Congenital Disorder of Glycosylation I (CDG-I)

Congenital Disorder of Glycosylation I (CDG-I) is a rare genetic disorder that affects the body's ability to properly synthesize sugar molecules. While there is no specific treatment for CDG-I, various therapeutic approaches have been explored to manage its symptoms and improve quality of life.

• Galactose Supplementation: One such treatment involves oral supplementation of galactose, which has shown promise in improving UDP-galactose supplies and reducing the severity of symptoms in some individuals with SLC35A2-CDG (a subtype of CDG-I) [1].
• Nutritional Therapies: Nutritional therapies, including dietary modifications and supplements, have been used to manage various aspects of CDG-I, such as gastrointestinal issues and liver disease [3].
• Gene Therapy: Researchers are exploring gene therapy approaches to correct the underlying genetic defect in glycosylation that causes CDG-I. While still in its infancy, this approach holds promise for future treatment options [2].
• Supportive Care: For many individuals with CDG-I, supportive care is essential to manage symptoms and prevent complications. This may include regular follow-up appointments with a gastroenterologist/hepatologist to monitor liver function and address any related issues [3].

Current Research and Developments

Recent studies have focused on developing targeted therapies for specific subtypes of CDG-I, such as MPI-CDG, SLC35C1-CDG, PIGM-CDG, and PGM1-CDG. Additionally, researchers are investigating the use of substrate replacement therapy with mannose-1-phosphate (GLM101) to treat CDG-I [4].

References

[1] JH Park et al. (2021). Galactose supplementation for SLC35A2-CDG: A promising treatment approach? [1]

[2] IJ Chang et al. (2018). Treatment for glycosylation defects: A review of current approaches. [6]

[3] J Verheijen et al. (2020). Nutritional therapies and transplantation in CDG: A summary of successful clinical applications. [3]

[4] M Monticelli et al. (2023). Substrate replacement therapy with mannose-1-phosphate for CDG-I: A new treatment option? [8]

The differential diagnosis for Congenital Disorders of Glycosylation (CDG) involves a range of metabolic and hormonal disorders that can present with similar symptoms.

• Metabolic disorders: CDG can be confused with other metabolic disorders such as Pompe disease, Fabry disease, and Gaucher disease [10].
• Hormonal disorders: The condition can also be misdiagnosed as hormonal disorders like hypothyroidism or adrenal insufficiency [9].
• Other conditions: Other conditions that may present with similar symptoms include:
  • Pompe disease: A genetic disorder caused by the deficiency of acid alpha-glucosidase, leading to glycogen accumulation in muscles [10].
  • Fabry disease: A genetic disorder caused by the deficiency of alpha-Galactosidase A, leading to the accumulation of globotriaosylsphingosine (Lyso-Gb3) in tissues [9].
  • Gaucher disease: A genetic disorder caused by the deficiency of glucocerebrosidase, leading to the accumulation of glucocerebroside in macrophages [10].

It's worth noting that CDG is a rare and complex condition, and accurate diagnosis often requires a combination of clinical evaluation, laboratory tests, and genetic analysis.

References: [9] by M Greczan · 2022 · Cited by 1 [10] by S Rani · 2023 · Cited by 1