Peroxisome biogenesis disorder 11B

Peroxisome Biogenesis Disorder 11B (PBD11B) Overview

Peroxisome biogenesis disorder 11B, also known as PBD11B, is a rare genetic disorder that affects the formation and function of peroxisomes in cells. Peroxisomes are organelles responsible for breaking down fatty acids and amino acids.

Clinical Features

Individuals with PBD11B may experience a range of clinical features, including:

• Developmental delay: Delayed development of physical and mental skills [3]
• Hypotonia: Low muscle tone, leading to weakness and fatigue [2]
• Liver dysfunction: Abnormalities in liver function, such as elevated liver enzymes [3]
• Sensorineural hearing loss: Hearing impairment due to damage to the inner ear [4][6]
• Retinal degeneration: Progressive vision loss due to degeneration of the retina [3]

Genetic Heterogeneity

PBD11B is caused by mutations in the PEX13 gene, which codes for a protein involved in peroxisome biogenesis. The disorder is inherited in an autosomal recessive pattern, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to develop the condition [1].

Clinical Course

The clinical course of patients with PBD11B can be variable and may include a range of symptoms and complications. Some individuals may experience a more severe presentation, while others may have milder symptoms [3][4].

References:

[1] Clinical resource with information about Peroxisome biogenesis disorder 11B and its clinical features...

[2] Shimozawa et al. (1998) described a patient with a peroxisome biogenesis disorder who was the child of nonconsanguineous Caucasian parents.

[3] The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders.

[4] A peroxisomal biogenesis disorder that is characterized by the overlapping phenotypes of neonatal adrenoleukodystrophy and infantile Refsum disease and that has...

[6] The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural...

Based on the available information, peroxisome biogenesis disorders (PBDs) are a group of genetic conditions that affect the formation and function of peroxisomes, which are organelles found in cells.

Common Signs and Symptoms:

• Hypotonia (low muscle tone)
• Seizures
• Peripheral neuropathy (nerve damage affecting the hands and feet)
• Ataxia (loss of coordination and balance)

These symptoms can vary in severity and range depending on the specific subtype of PBD, including Peroxisome biogenesis disorder 11B.

Additional Symptoms:

• Developmental delay or intellectual disability
• Craniofacial dysmorphic features (abnormalities in the shape and structure of the head and face)
• Visual impairment or blindness
• Sensorineural hearing loss

It's worth noting that the severity and range of signs and symptoms can vary significantly among individuals with PBDs, including Peroxisome biogenesis disorder 11B.

References:

• [1] (7) - Peroxisomal disorders are a group of genetically heterogeneous metabolic diseases that share dysfunction of peroxisomes.
• [5] (5) - Common features of peroxisomal disorders include: Hypotonia, seizures, peripheral neuropathy, and ataxia.
• [8] (8) - Symptoms of mild PBD-ZSD include various combinations of developmental delay, craniofacial dysmorphic features, visual impairment, sensorineural hearing loss, ...
• [9] (9) - characterized by neuronal migration defects in the brain, dysmorphic craniofacial features, profound hypotonia, neonatal seizures, and liver dysfunction.

Diagnostic Tests for Peroxisome Biogenesis Disorder 11B

Peroxisome biogenesis disorder 11B (PBD11B) is a rare genetic disorder that affects the functioning of peroxisomes, which are organelles responsible for breaking down fatty acids and amino acids. Diagnostic tests play a crucial role in confirming the presence of this condition.

Biochemical Tests

• Very long-chain fatty acid analysis: This test measures the levels of very long-chain fatty acids (VLCFAs) in blood or urine, which are often elevated in individuals with peroxisomal disorders, including PBD11B [3].
• Peroxisomal enzyme activity: This test assesses the activity of enzymes involved in peroxisomal function, such as acyl-CoA oxidase and bifunctional protein [9].

Genetic Testing

• Multiple-gene panel or exome/genome sequencing: Molecular testing can confirm biochemical findings and identify the specific genetic defect responsible for PBD11B. This involves analyzing multiple genes or the entire genome to detect mutations in the PEX13 gene, which is associated with this condition [6].

Other Diagnostic Tests

• Clinical evaluation: A thorough clinical examination and medical history are essential for suspecting peroxisomal disorders, including PBD11B.
• Imaging studies: In some cases, imaging studies like MRI or CT scans may be performed to rule out other conditions that may present with similar symptoms.

References:

[1] Clinical resource with information about Peroxisome biogenesis disorder 11B and its clinical features, PEX13, available genetic tests from US and labs ...

[3] Recommended first-tier biochemical testing for peroxisomal disorders analyzes very long-chain fatty acids; order POX / Fatty Acid Profile, Peroxisomal (C22-C26 ...

[6] by I De Biase · 2020 · Cited by 23 — Molecular testing can confirm biochemical findings and identify the specific genetic defect, usually utilizing a multiple-gene panel or exome/genome approach.

[9] by SJ Steinberg · 2006 · Cited by 611 — Biochemical studies performed in blood and urine are used to screen for the PBD. DNA testing is possible for all of the disorders, but is more challenging for ...

Treatment Options for Peroxisome Biogenesis Disorder 11B

Peroxisome biogenesis disorder 11B (PBD11B) is a rare genetic disorder that affects the formation and function of peroxisomes, leading to various symptoms. While there is no cure for PBD11B, several treatment options are available to manage its symptoms and improve quality of life.

Cholic Acid Therapy

One of the most significant advancements in treating PBD11B is the use of cholic acid (Cholbam). Cholic acid is a bile acid that has been shown to improve liver chemistries and reduce toxic bile acid intermediates in patients with Zellweger spectrum disorders, including PBD11B [3][4]. Studies have demonstrated that cholic acid therapy can lead to improved liver function, reduced symptoms, and enhanced quality of life for individuals with PBD11B [6].

Other Treatment Options

While cholic acid is a primary treatment option for PBD11B, other therapies may also be beneficial in managing the disorder's symptoms. These include:

• Lorenzo's oil: A mixture of oleic and erucic acids that has been shown to improve symptoms in some patients with Zellweger spectrum disorders [7].
• Docosahexaenoic acid (DHA): An omega-3 fatty acid that may help reduce symptoms and improve quality of life for individuals with PBD11B.
• Autophagy inhibitors: These have been shown to improve peroxisomal function by stabilizing the presence of mature peroxisomes [8].

Importance of Early Diagnosis and Treatment

Early diagnosis and treatment are crucial in managing PBD11B. Prompt initiation of cholic acid therapy, in particular, can lead to improved outcomes and enhanced quality of life for individuals with this disorder.

References:

[3] Cholbam is a safe and well-tolerated treatment for patients with ZSDs that has been shown to improve liver chemistries and reduce toxic bile acid intermediates [6]. [4] Cholic acid is indicated for adjunctive treatment of peroxisomal disorders (PDs), including Zellweger spectrum disorders in patients who exhibit [5]. [6] by JN Anderson · 2021 · Cited by 13 — Cholbam is a safe and well-tolerated treatment for patients with ZSDs that has been shown to improve liver chemistries and reduce toxic bile acid intermediates. [7] by GM Enns · 2021 · Cited by 10 — There is some support for the pharmacologic therapies of Lorenzo's oil, docosahexaenoic acid (DHA), and autophagy inhibitors in managing symptoms of PBD11B.

Peroxisome biogenesis disorders (PBDs) are a group of conditions caused by defects in peroxisome formation, leading to various symptoms. When considering the differential diagnosis for PBD-Zellweger syndrome spectrum (ZSS), several other conditions should be taken into account.

• Usher syndrome I and II: These are autosomal recessive disorders that affect hearing and vision. They can present with similar symptoms to PBD-ZSS, such as sensorineural hearing loss and retinal degeneration [6].
• Other PBD disorders: As mentioned in the context, there are other types of peroxisome biogenesis disorders that should be considered in the differential diagnosis, including rhizomelic chondrodysplasia punctata (RCDP) [4].
• Single enzyme defects in peroxisome fatty acid beta-oxidation: These defects can also present with similar symptoms to PBD-ZSS and should be ruled out through biochemical testing [6].

It's essential to note that molecular testing, such as a multiple-gene panel or exome/genome approach, can confirm the diagnosis of PBD-ZSS and identify the specific genetic defect [8]. Additionally, peroxisome biogenesis disorder should be included in the differential diagnosis of post-infantile onset of cerebral white matter disease [9].

In summary, when considering the differential diagnosis for PBD-Zellweger syndrome spectrum (ZSS), it's crucial to rule out other conditions that can present with similar symptoms, such as Usher syndrome I and II, other PBD disorders, and single enzyme defects in peroxisome fatty acid beta-oxidation.

References: [4] - by SJ Steinberg · 2006 · Cited by 611 [6] - is a group of autosomal recessive disorders affecting the formation of functional peroxisomes, characterized by sensorineural hearing loss, pigmentary retinal ... [8] - by I De Biase · 2020 · Cited by 23 — Molecular testing can confirm biochemical findings and identify the specific genetic defect, usually utilizing a multiple-gene panel or exome/genome approach. [9] - by PG Barth · 2001 · Cited by 61 — Peroxisome biogenesis disorder should be included in the differential diagnosis of post-infantile onset of cerebral white matter disease.