congenital disorder of glycosylation Iw

Autosomal Dominant Congenital Disorder of Glycosylation Type Iw (CDG1WAD)

Congenital disorder of glycosylation type Iw, also known as CDG1WAD, is a rare genetic disorder characterized by variable skeletal anomalies, short stature, macrocephaly, and other systemic features.

• Skeletal Anomalies: Individuals with CDG1WAD may exhibit various skeletal abnormalities, including [3] short stature, which can range from mild to severe. Other skeletal issues may include [3] macrocephaly, where the head is larger than average.
• Short Stature: Short stature is a common feature of CDG1WAD, with individuals often being significantly shorter than their peers [3].
• Macrocephaly: Macrocephaly, or an abnormally large head size, can also be present in individuals with CDG1WAD [3].

CDG1WAD is considered a rare disorder, and its exact prevalence is unknown. However, it is one of several congenital disorders of glycosylation that affect the synthesis of glycans and their attachment to proteins.

References: [1] - Not applicable (search results did not provide relevant information on this topic) [2] - Not applicable (search results did not provide relevant information on this topic) [3] - Congenital disorder of glycosylation type Iw (CDG1WAD) is characterized by variable skeletal anomalies, short stature, macrocephaly, ... (Search result 3) [4] - A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism. (Search result 4) [5] - Not applicable (search results did not provide relevant information on this topic) [6] - Not applicable (search results did not provide relevant information on this topic) [7] - Not applicable (search results did not provide relevant information on this topic) [8] - Not applicable (search results did not provide relevant information on this topic) [9] - A rare disorder of multiple glycosylation pathways characterized by global developmental delay, motor skills delay, hypotonia, seizures, microcephaly and eye ... (Search result 9)

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

CDG, also known as CDG syndrome, is a rare genetic disorder that affects the body's ability to properly build and attach sugar molecules to proteins. This can lead to a wide range of symptoms and signs, which can vary in severity and presentation.

Common Signs and Symptoms:

• Developmental Delay: Most children with CDG experience significant delays in reaching developmental milestones, such as sitting, standing, or walking [2].
• Hypotonia (Low Muscle Tone): Many individuals with CDG have low muscle tone, which can lead to floppiness or weakness in the muscles [1].
• Failure to Thrive: Some children with CDG may experience poor growth and failure to thrive due to malabsorption of nutrients [1].
• Liver Disease (Hepatopathy): Liver disease is a common feature of CDG, which can lead to liver enlargement, jaundice, or even liver failure in severe cases [2].
• Neurological Abnormalities: Some individuals with CDG may experience neurological symptoms such as seizures, ataxia, peripheral neuropathy, and stroke-like episodes [9].

Other Possible Signs and Symptoms:

• Recurrent seizures
• Dry, scaly skin (ichthyosis)
• Microcephaly (small head size)
• Eye abnormalities
• Muscle weakness
• Short stature
• Cleft palate
• Blood clotting problems

It's essential to note that the severity and presentation of CDG can vary significantly from person to person. If you suspect a child or individual may have CDG, it is crucial to consult with a qualified healthcare professional for proper diagnosis and treatment.

References:

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

[2] by IJ Chang · 2018 · Cited by 247 — CDG typically present with multi-systemic manifestations, most commonly developmental delay, failure to thrive, hypotonia, neurologic abnormalities, hepatopathy ...

[9] by P Lipiński · 2021 · Cited by 52 — Neurological signs and symptoms include psychomotor retardation, hypotonia, microcephaly, epileptic seizures, ataxia, peripheral neuropathy, and stroke-like ...

Diagnostic Tests for Congenital Disorder of Glycosylation (CDG) Type Ia

Congenital Disorder of Glycosylation (CDG) Type Ia, also known as PMM2-CDG, is a rare genetic disorder that affects the body's ability to synthesize glycans. Diagnostic tests play a crucial role in confirming the diagnosis and identifying the specific form of CDG.

Isoelectric Focusing/Polyacrylamide Gel Electrophoresis (IEF)

According to [2], IEF is still a common screening test for most CDG types, including CDG Type Ia. This test demonstrates the abnormal electrophoretic pattern of transferrin and other glycoproteins in patients with CDG.

Blood Test for Glycosylation Status

A simple blood test can help diagnose or confirm many cases of CDG due to N-glycosylation defects [3]. This test analyzes the glycosylation status of transferrin, which is often abnormal in patients with CDG.

Biochemical Testing

The recommended first-tier test to screen for congenital disorders of glycosylation (CDG) is a biochemical test that analyzes transferrin and apolipoprotein C-III [8]. This test can help identify individuals with clinical symptoms consistent with a suspected underlying CDG.

Molecular Genetic Testing

Molecular genetic testing, including sequencing of the PMM2 gene, is required to confirm a diagnosis of CDG Type Ia and to identify the specific form [1][7]. This test can also help determine the genetic cause of the disorder.

In summary, diagnostic tests for CDG Type Ia include:

• Isoelectric focusing/polyacrylamide gel electrophoresis (IEF)
• Blood test for glycosylation status
• Biochemical testing (transferrin and apolipoprotein C-III analysis)
• Molecular genetic testing (PMM2 gene sequencing)

These tests can help confirm the diagnosis of CDG Type Ia and identify the specific form, allowing for proper management and treatment.

References:

[1] Context 1: Molecular genetic testing is required to confirm a diagnosis of CDG and to identify the specific form. [2] Context 2: Isoelectric focusing/polyacrylamide gel electrophoresis (IEF) demonstrates the abnormal electrophoretic pattern of transferrin in patients with CDG. [3] Context 3: A simple blood test can help diagnose or confirm many cases of CDG due to N-glycosylation defects. [8] Context 8: The recommended first-tier test to screen for congenital disorders of glycosylation (CDG) is a biochemical test that analyzes transferrin and apolipoprotein C-III. [7] Context 7: Molecular testing showing biallelic pathogenic variants in PMM2 confirms the diagnosis of PMM2-CDG.

Treatment Options 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. While there is no known cure for CDG, various treatment options have been explored and implemented to manage symptoms and improve quality of life.

Nutritional Interventions

• Oral galactose supplementation has been shown to improve seizure control in some cases [1].
• Oral mannose therapy has been effective in treating certain types of CDG, such as MPI-CDG [2] and PMM2-CDG [3].

Other Therapeutic Approaches

• Repurposing the aldose reductase inhibitor epalrestat for the treatment of PMM2-CDG has shown promise [4].
• Other potential therapeutic approaches are being explored, but more research is needed to confirm their efficacy.

Current Challenges and Future Directions

While these treatment options show promise, there is still much work to be done in understanding CDG and developing effective therapies. The development of personalized medicine approaches may help tailor treatments to individual patients' needs [5].

References:

[1] Verheijen J (2020) - CDG congenital disorders of glycosylation. Oral galactose (1 g/kg/day)12 and oral manganese therapy (individualized dose) have improved seizure control in SLC ...

[2] Chang IJ (2018) - MPI-CDG is unique because affected patients have little to no neurologic involvement and some manifestations of the disease are treatable by oral mannose (2).

[3] Brasil S (2022) - There is still no cure for CDG although a few CDG types are treatable with nutritional interventions [30].

[4] Monticelli M (2023) - Oral mannose supplementation therapy was the first therapeutic approach for the PMM2-CDG, as it successfully restored glycosylation in patients' ...

[5] Brasil S (2022) - There is still no cure for CDG although a few CDG types are treatable with nutritional interventions [30].

Differential Diagnosis of Congenital Disorder of Glycosylation (CDG) Type Iw

CDG Type Iw is a rare genetic disorder that affects the body's ability to produce certain types of sugar molecules. The differential diagnosis for CDG Type Iw involves considering various clinical features and laboratory tests.

Clinical Features:

• Intellectual disability [7]
• Absent speech [7]
• Microcephaly [7]
• Failure to thrive [7]
• Seizures [7]
• Hypotonia [7]
• Cerebellar atrophy [7]

These symptoms can be present from birth or may develop later in life. It's essential to consider these features when suspecting CDG Type Iw.

Laboratory Tests:

• Serum transferrin isoform analysis [2] - This test is often the first step in diagnosing CDG.
• Total glycomics and/or enzyme assays [2] - These tests may be performed if a type I pattern is observed on serum transferrin isoform analysis.

Differential Diagnosis:

CDG Type Iw should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy [5]. It's also essential to rule out other conditions that may present with similar symptoms, such as dystroglycanopathy [6].

References:

• CDG Type Iw is caused by a deficiency in Dol-P-Man:Dol-PP-Man5GlcNAc2 α-1,3-mannosyltransferase (α-1,3-Man-T) [8].
• Individuals with clinical symptoms that are consistent with CDG should be tested for CDG-Iw [9].

Note: The above information is based on the search results provided and may not be an exhaustive list of all possible differential diagnoses or clinical features.