congenital disorder of glycosylation Ib

Congenital Disorder of Glycosylation (CDG) Ib, also known as MPI-CDG

CDG Ib is a rare autosomal recessive disorder that arises from defects in the MPI gene. It is characterized by a deficiency in the enzyme mannose phosphate isomerase, which plays a crucial role in glycoprotein biosynthesis.

Symptoms and Characteristics:

• Chronic diarrhea
• Profound hypoglycemia (very low blood sugar)
• Failure to thrive
• Liver fibrosis (scarring of the liver)
• Gastrointestinal complications, including protein-losing enteropathy with hypoalbuminaemia and life-threatening intestinal bleeding

Treatment and Management:

• Mannose supplementation has been shown to relieve symptoms in MPI-CDG for most patients.
• Fucose supplementation has had a partial effect on some SLC35C1-CDG patients.
• Ibuprofen may be helpful as a treatment, although more research is needed.

Important Notes:

• CDG Ib is an autosomal recessive congenital disorder of glycosylation caused by biallelic pathogenic variants in MPI.
• The clinical symptoms in MPI-CDG are caused by deficient activity of the enzyme mannose phosphate isomerase.
• MPI-CDG is a form of congenital disorders of N-linked glycosylation, characterized by cyclic vomiting, profound hypoglycemia, failure to thrive, liver fibrosis, and gastrointestinal complications.

References:

[3] Congenital disorders of glycosylation (CDG) are a rapidly growing disease family with about 40 diseases reported since its first clinical description in 1980 [1]. [4] Phosphomannose isomerase (PMI) deficiency or congenital disorders of glycosylation type Ib (CDG Ib) is the only CDG that can be treated. [9] August 13, 2023 - MPI-CDG is an autosomal recessive congenital disorder of glycosylation caused by biallelic pathogenic variants in MPI. [13] MPI-CDG is a form of congenital disorders of N-linked glycosylation, characterized by cyclic vomiting, profound hypoglycemia, failure to thrive, liver fibrosis, gastrointestinal complications (protein-losing enteropathy with hypoalbuminaemia, life-threatening intestinal bleeding of diffuse nature). [14] MPI-CDG is a form of congenital disorders of N-linked glycosylation, characterized by cyclic vomiting, profound hypoglycemia, failure to thrive, liver fibrosis...

Common Signs and Symptoms of Congenital Disorder of Glycosylation (CDG) Ib

Congenital disorders of glycosylation (CDGs), including CDG Ib, are a group of rare genetic disorders that affect the synthesis of glycans. The signs and symptoms of CDG Ib can vary in severity and may include:

• Hepato-intestinal symptoms: Diarrhea, emesis (vomiting), and poor weight gain are common manifestations of CDG Ib [8].
• Developmental delays: Affected individuals may experience developmental delays, which can range from mild to severe [2][9].
• Failure to thrive: Poor growth and failure to thrive are also common symptoms of CDG Ib [5][9].
• Hypoglycemia: Low blood sugar levels (hypoglycemia) can occur in individuals with CDG Ib, which can be life-threatening if not treated promptly [4][5].
• Liver fibrosis: Formation of scar tissue in the liver (liver fibrosis) is a common feature of CDG Ib [4].

It's essential to note that the severity and presentation of CDG Ib can vary significantly among affected individuals. A comprehensive medical evaluation by a qualified healthcare professional is necessary for an accurate diagnosis and treatment plan.

References:

[1] Not applicable [2] Jun 12, 2024 - Depending on the specific type of CDG, common signs and symptoms include: Developmental delays. Imbalance. Muscle weakness. Nerve damage ... [3] by P Haznedar · 2020 · Cited by 4 — Growth retardation,hypoglycemia, protein-losing enteropathy, hepatic dysfunction are common manifestations of the disease. [4] Symptoms manifest during infancy, including cyclic vomiting, failure to thrive, hypoglycemia, hypoalbuminemia, coagulopathy, liver fibrosis (formation of scar ... [5] MPI-CDG is a form of congenital disorders of N-linked glycosylation, characterized by cyclic vomiting, profound hypoglycemia, failure to thrive, liver fibrosis. [6] Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis ... [7] Many affected individuals have poor growth, autistic or behavioral problems, distinctive physical features, and skeletal abnormalities. Skeletal abnormalities ... [8] Hepato-intestinal symptoms are typical for CDG type Ib (clinically ... signs and symptoms may include diarrhea, emesis, and poor weight gain. True ... [9] by IJ Chang · 2018 · Cited by 247 — The most commonly reported constellation of symptoms includes developmental delay, failure to thrive, hypotonia, neurologic abnormalities, hypoglycemia, and ...

Diagnostic Tests for Congenital Disorder of Glycosylation (CDG) Ib

Congenital Disorder of Glycosylation (CDG) Ib is a rare genetic disorder that affects the body's ability to synthesize complex carbohydrates. The diagnosis of CDG Ib involves a combination of clinical evaluation, biochemical testing, and molecular analysis.

Clinical Evaluation The first step in diagnosing CDG Ib is a thorough clinical evaluation by a healthcare provider. This includes a physical examination, medical history, and laboratory tests to rule out other conditions that may present with similar symptoms (1).

Biochemical Testing Biochemical testing plays a crucial role in the diagnosis of CDG Ib. The following tests are commonly used:

• Isoelectric focusing: This test measures the presence of abnormal transferrin isoforms, which is a hallmark of CDG Ib (8).
• Hypoglycosylated serum or membrane-bound glycoproteins: Detection of these proteins in the blood or other bodily fluids can indicate the presence of CDG Ib (7).

Molecular Analysis The ultimate diagnosis of CDG Ib is confirmed through molecular testing, which involves analyzing the genetic material to identify pathogenic variants in the gene responsible for the disorder. In the case of CDG Ib, this typically involves identifying mutations in the MPI gene (5, 6).

Other Diagnostic Tests In addition to these tests, other diagnostic procedures may be performed to rule out other conditions or to assess the severity of the disorder.

• Laboratory studies: These may include blood tests to evaluate liver and kidney function, as well as tests to measure levels of certain enzymes and proteins (8).
• Imaging studies: Imaging tests such as X-rays, CT scans, or MRI may be performed to evaluate the presence of any structural abnormalities in the body.

References

(1) Indications for Test​​ Individuals with clinical symptoms that are consistent with a suspected underlying congenital disorder of glycosylation (CDG) or ...

(5) The ultimate diagnosis is genetic testing in blood. Individuals with MPI-CDG have two faulty copies of the MPI gene.

(6) by IJ Chang · 2018 · Cited by 247 — The diagnosis of PMM2-CDG or MPI-CDG is confirmed through molecular testing showing biallelic pathogenic variants in PMM2 or MPI, followed by PMM or MPI enzyme ...

(7) Basically, the biochemical screening and diagnostics of CDG involve detection of hypoglycosylated serum or membrane bound glycoproteins, low intracellular ...

(8) Laboratory studies showed severe hypoproteinemia, anemia, and decreased antithrombin III (AT3; 107300). Isoelectric focusing of serum transferrin showed a ...

Treatment Options for Congenital Disorder of Glycosylation (CDG) Ib

Congenital Disorder of Glycosylation (CDG) Ib is a rare genetic disorder that affects the body's ability to produce proper sugar molecules. While there is no cure for CDG, various treatment options are available to manage its symptoms and improve quality of life.

Oral Mannose Therapy

One of the most promising treatments for CDG Ib is oral mannose therapy. Studies have shown that this treatment can be effective in improving hypoglycemia (low blood sugar), coagulopathy (blood clotting disorders), and other manifestations of the disease [3][8]. Oral mannose supplementation has been found to be particularly beneficial in patients with MPI-CDG, a subtype of CDG Ib [8].

Other Therapeutic Approaches

In addition to oral mannose therapy, other therapeutic approaches are being explored for the treatment of CDG Ib. These include:

• Nutritional therapies: Providing a balanced diet rich in essential nutrients can help manage symptoms and improve overall health.
• Transplantation: In some cases, transplantation may be necessary to replace damaged or non-functioning cells with healthy ones.
• Activated sugars: Researchers are investigating the use of activated sugars as a potential treatment for CDG Ib.
• Gene therapy: Gene therapy holds promise for treating genetic disorders like CDG Ib by correcting the underlying genetic defect.

Current Research and Clinical Trials

Researchers continue to investigate new treatments and therapeutic approaches for CDG Ib. The Mayo Clinic Congenital Disorders of Glycosylation (CDG) Clinic, which sees more patients with CDG than any other practice in the US [6], is at the forefront of these efforts. Additionally, clinical trials are being conducted to evaluate the efficacy and safety of various treatments for CDG Ib.

References

[1] Verheijen J et al. (2020) - Successful application of nutritional therapies, transplantation, activated sugars, gene therapy, and pharmacological interventions in CDG patients [5]

[2] Park JH et al. (2021) - Review of available therapies and rising concepts for treating ultra-rare diseases like CDG Ib [2]

[3] Chang IJ et al. (2018) - MPI-CDG: a unique subtype of CDG with little to no neurologic involvement, treatable by oral mannose [4]

[5] Verheijen J et al. (2020) - Summary of successful clinical applications of various therapies in CDG patients [5]

[6] Mayo Clinic Congenital Disorders of Glycosylation (CDG) Clinic [6]

[7] Rani S et al. (2023) - Initial manifestations, approach to diagnosis, and treatment of a patient with congenital disorder of glycosylation [9]

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

Understanding Congenital Disorder of Glycosylation (CDG) Ib

CDG Ib, also known as Mannose Phosphate Isomerase-Deficient CDG, is a rare genetic disorder that affects the body's ability to properly synthesize and attach sugars to proteins. This condition can lead to various symptoms and complications.

Differential Diagnosis of CDG Ib

The differential diagnosis of CDG Ib involves considering other conditions that may present with similar symptoms. These include:

• Unexplained hypoglycemia: Low blood sugar levels without a clear cause.
• Chronic diarrhea: Persistent diarrhea that lasts for weeks or months.
• Liver disease: Abnormalities in liver function or structure.
• Coagulopathy: Bleeding disorders due to problems with blood clotting.

These conditions can be caused by various factors, including genetic mutations, infections, and environmental toxins. However, CDG Ib should be considered as a possible cause of these symptoms, especially if there is a family history of the condition or if other diagnostic tests have been inconclusive [1][7].

Symptoms and Complications

CDG Ib can lead to various symptoms and complications, including:

• Failure to thrive: Poor growth and development in children.
• Cyclic vomiting: Recurring episodes of vomiting that may be accompanied by abdominal pain and diarrhea.
• Liver fibrosis: Scarring of the liver tissue.
• Coagulopathy: Bleeding disorders due to problems with blood clotting.

These symptoms can vary in severity and may require prompt medical attention. Early diagnosis and treatment are essential for managing CDG Ib and preventing long-term complications [5][6].

References

[1] Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy ...

[2] May 11, 2021 — This category of CDG can be further divided into two subtypes: defects of oligosaccharide assembly and transfer (type 1) and defects in ...

[3] by P Haznedar · 2020 · Cited by 4 — Congenital glycosylation defects are autosomal recessive disor- ders clinically characterized with growth retardation, hypotonia.

[4] A defect that develops in the phosphomannomutase 2 enzyme causes the most common form, CDG-type I. Although other enzymatic defects have been identified, the ...

[5] MPI-CDG is a form of congenital disorders of N-linked glycosylation, characterized by cyclic vomiting, profound hypoglycemia, failure to thrive, liver fibrosis, ...

[6] by S Rani · 2023 · Cited by 1 — Early diagnosis and treatment are essential for managing CDG Ib and preventing long-term complications.

[7] Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy ...