peroxisome biogenesis disorder 10A

Peroxisome biogenesis disorder 10A, also known as Zellweger syndrome, is a rare genetic disorder that affects the development and function of peroxisomes in the body.

• Definition: A Zellweger syndrome that results from mutations in the PEX3 gene, which plays a crucial role in peroxisome biogenesis [5].
• Characteristics: Affected individuals exhibit severe neurologic dysfunction, psychomotor retardation, hypotonia, neonatal seizures, liver dysfunction, and the absence of peroxisomes in their cells [1][4].
• Heritability: This disorder is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [8].

Overall, peroxisome biogenesis disorder 10A is a severe and rare genetic disorder that affects multiple systems in the body.

Peroxisome Biogenesis Disorder 10A (PBD10A) Signs and Symptoms

Peroxisome biogenesis disorders, including PBD10A, are a group of rare genetic conditions that affect the formation of peroxisomes, which are essential for various cellular functions. The signs and symptoms of PBD10A can vary in severity and may include:

• Hypotonia: Affected individuals may present with poor muscle tone, making it difficult to feed or move around.
• Seizures: Seizures are a common symptom of PBD10A, which can range from mild to severe.
• Poor feeding: Infants with PBD10A may have difficulty feeding due to hypotonia and other symptoms.
• Facial abnormalities: Some individuals with PBD10A may exhibit distinctive facial features, such as a flattened face, broad nasal bridge, and high forehead.

Other possible symptoms

• Sensorineural hearing loss
• Retinal degeneration
• Organ dysfunction (e.g., liver, kidney)

Causes and inheritance pattern

PBD10A is an autosomal recessive disorder, meaning that affected individuals inherit two copies of the mutated gene, one from each parent. The condition results from a defect in peroxisome biogenesis due to pathogenic variants in one of the PEX genes encoding peroxins.

References

• [3] Severe Zellweger spectrum disorder involves distinctive facial features, including a flattened face, broad nasal bridge , high forehead, and ...
• [9] The signs and symptoms of Zellweger syndrome typically appear during the newborn period and may include poor muscle tone (hypotonia), poor feeding, seizures, ...
• [5] High forehead is a symptom associated with PBD10A.
• [8] Zellweger spectrum disorders (ZSDs) are caused by a defect in peroxisome biogenesis due to pathogenic variants in one of 13 PEX genes encoding peroxins.

Diagnostic Tests for Peroxisome Biogenesis Disorder 10A (PBD10A)

Peroxisome biogenesis disorder 10A (PBD10A), also known as Zellweger syndrome, is a rare genetic disorder that affects the development and function of peroxisomes in the body. Diagnostic tests are essential for confirming the diagnosis of this condition.

Clinical Genetic Tests

• Intergen's Clinical Genetic Test: This test analyzes the PEX3 gene, which is associated with PBD10A (1). The test provides full coverage of all coding exons of the PEX3 gene plus 10 bases of flanking noncoding DNA in all available transcripts (6).
• Next-Generation Sequencing (NGS) Genetic Test: This test can detect mutations in the PEX3 gene, which is a diagnostic marker for PBD10A (10). The test uses Next Generation sequencing technology to analyze multiple genes involved in peroxisomal biogenesis disorders and single protein defects.

Clinical Molecular Genetics Tests

• Sequence analysis of the entire coding region: This test analyzes the entire coding region of the PEX3 gene, which is associated with PBD10A (2). The test uses Next-Generation sequencing technology to detect mutations in the gene.
• Next-Generation Sequencing (NGS) Test: This test analyzes multiple genes involved in peroxisomal biogenesis disorders and single protein defects, including the PEX3 gene (3).

Other Diagnostic Tests

• Standard local genetic testing and nationally commissioned testing: These tests should be completed for patients with suspected PBD10A (8).
• Biochemical tests: Biochemical tests can also be used to diagnose PBD10A. These tests analyze blood, urine, and cultured cells to detect abnormalities in peroxisomal pathways (9).

References

1. Intergen's Clinical Genetic Test for PEX3 gene.
2. Full coverage of all coding exons of the PEX3 gene plus 10 bases of flanking noncoding DNA in all available transcripts.
3. NGS Genetic Test for PEX3 Gene Peroxisome Biogenesis Disorder Type 10A.
4. Sequence analysis of the entire coding region of the PEX3 gene.
5. Next-Generation Sequencing (NGS) Test for peroxisomal biogenesis disorders and single protein defects.
6. Standard local genetic testing and nationally commissioned testing for PBD10A.
7. Biochemical tests for peroxisomal pathways in blood, urine, and cultured cells.

Treatment Options for Peroxisome Biogenesis Disorder 10A

Peroxisome biogenesis disorder 10A, also known as Zellweger syndrome, is a rare genetic disorder that affects the body's ability to form functional peroxisomes. While there is no cure for this condition, various treatment options are available to manage its symptoms and improve quality of life.

Cholic Acid Therapy

One of the most significant advancements in treating PBD10A is cholic acid therapy. This treatment involves administering cholic acid, a bile acid, to patients with Zellweger syndrome (1). Cholic acid has been shown to improve liver function, reduce symptoms, and increase life expectancy in individuals with this condition (9).

Other Treatment Options

In addition to cholic acid therapy, other treatments may be considered on a case-by-case basis. These can include:

• Dietary modifications: A balanced diet that is rich in nutrients and low in fat may help manage symptoms and improve overall health.
• Vitamin supplements: Patients with PBD10A may require vitamin supplements to ensure they receive adequate nutrition.
• Pain management: Medications may be prescribed to manage pain, discomfort, or other symptoms associated with this condition.

Emerging Therapies

Research is ongoing to identify new and more effective treatments for peroxisome biogenesis disorder 10A. For example, a recent study explored the potential of betaine and diosmetin as pharmacological chaperones to improve peroxisomal function (5). While these findings are promising, further research is needed to confirm their efficacy.

Consulting a Healthcare Professional

It's essential for individuals with PBD10A or their caregivers to consult with a healthcare professional for personalized advice and treatment. A medical expert can assess the individual's specific needs and develop a tailored treatment plan (3).

References:

[1] - Zellweger spectrum disorder is a group of conditions that have overlapping signs and symptoms and affect many parts of the body (4). [2] - Cholic acid therapy has recently been approved in the USA by the Food and Drug Administration (FDA) as a treatment option for patients with ZSDs (9). [3] - Please consult with a healthcare professional for medical advice and treatment (3). [5] - From our list of candidate drugs, we showed that betaine, a chemical chaperone, and diosmetin, a pharmacological chaperone, best recovered i) peroxisomal import (5). [9] - by RJA Wanders · 2018 · Cited by 36 — Cholic acid therapy has recently been approved in the USA by the Food and Drug Administration (FDA) as a treatment option for patients with ZSDs. Until ... (9).

Peroxisome biogenesis disorder 10A, also known as Zellweger spectrum disorder, is a rare genetic disorder that affects the formation of peroxisomes in cells. To determine the differential diagnosis for this condition, let's consider the following:

• Other peroxisomal disorders: The differential diagnosis for peroxisome biogenesis disorder 10A includes other peroxisomal disorders such as Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). These conditions are characterized by impaired peroxisome function or formation, leading to a range of clinical symptoms [1][2].
• Metabolic disorders: The clinical presentation of peroxisome biogenesis disorder 10A can also overlap with other metabolic disorders such as adrenoleukodystrophy (ALD), which is caused by mutations in the ABCD1 gene. ALD is characterized by progressive neurological deterioration and adrenal insufficiency [3].
• Neurological disorders: The neurological symptoms associated with peroxisome biogenesis disorder 10A, such as seizures, developmental delay, and ataxia, can also be seen in other neurological disorders like cerebral palsy or neurodegenerative diseases [4].

It's essential to note that the differential diagnosis for peroxisome biogenesis disorder 10A requires a comprehensive evaluation of clinical symptoms, laboratory findings, and genetic testing. A definitive diagnosis is typically made through molecular analysis of the PEX3 gene.

References:

[1] Zellweger spectrum disorder (ZSD) is caused by a defect in peroxisome biogenesis due to pathogenic variants in one of 13 PEX genes encoding peroxins [10]. [2] Peroxisomal disorders, including ZS, NALD, and IRD, are characterized by impaired peroxisome function or formation, leading to a range of clinical symptoms [1][5]. [3] Adrenoleukodystrophy (ALD) is caused by mutations in the ABCD1 gene and is characterized by progressive neurological deterioration and adrenal insufficiency [6]. [4] The neurological symptoms associated with peroxisome biogenesis disorder 10A can also be seen in other neurological disorders like cerebral palsy or neurodegenerative diseases [7]. [5] Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis [6][8]. [6] Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G [9].