Peroxisome biogenesis disorder 8B

Peroxisome Biogenesis Disorder 8B (PBD8B) Clinical Features

Peroxisome biogenesis disorder 8B, also known as PBD8B, is a rare genetic disorder that affects the formation and function of peroxisomes in cells. The clinical features of PBD8B can vary, but they often include:

• Developmental delay: Individuals with PBD8B may experience delayed development, including delays in sitting, standing, and walking [2].
• Hypotonia: Muscle weakness or hypotonia is a common feature of PBD8B, which can lead to difficulties with motor skills and coordination [3].
• Liver dysfunction: Liver problems are also associated with PBD8B, including liver enlargement and dysfunction [4].
• Sensorineural hearing loss: Some individuals with PBD8B may experience hearing loss due to damage to the inner ear [5].
• Retinal dystrophy: Vision impairment or retinal dystrophy can occur in some cases of PBD8B [6].

Genetic Heterogeneity

Peroxisome biogenesis disorders, including PBD8B, are caused by mutations in genes involved in peroxisome formation. The genetic heterogeneity of PBD(NALD/IRD) means that different individuals may have mutations in different genes, leading to varying clinical features [1].

References:

[1] Clinical resource with information about Peroxisome biogenesis disorder 8B and its clinical features...

[2] Symptoms vary and may involve developmental delay, hypotonia, liver dysfunction, hearing loss, retinal dystrophy, and visual impairment.

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

[4] Symptoms vary and may involve developmental delay, hypotonia, liver dysfunction, hearing loss, retinal dystrophy, and visual impairment.

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

[6] Symptoms vary and may involve developmental delay, hypotonia, liver dysfunction, hearing loss, retinal dystrophy, and visual impairment.

Based on the provided context, here are the signs and symptoms of Peroxisome Biogenesis Disorder (PBD) 8B:

• Developmental delay: Patients may experience delays in reaching developmental milestones [4].
• Hypotonia: Affected individuals often present with profound hypotonia, which is a condition characterized by low muscle tone [3], [8].
• Liver dysfunction: PBD 8B can lead to liver dysfunction, which may manifest as decreased liver function or other related issues [2], [4].
• Hearing loss: Some patients may experience hearing loss as part of their symptoms [4].
• Retinal dystrophy: Visual impairment and retinal dystrophy (a condition affecting the retina) have been reported in individuals with PBD 8B [4].

It's worth noting that the severity and range of signs and symptoms can vary among affected patients, depending on the subgroup and age at presentation [6].

Diagnostic Tests for Peroxisome Biogenesis Disorder 8B

Peroxisome biogenesis disorder 8B (PBD 8B) 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 identifying this condition.

Clinical Molecular Genetics Test A clinical molecular genetics test can help identify PBD 8B by analyzing the entire coding region of the PEX16 gene using Next-Generation Sequencing (NGS) technology [2]. This test is specifically designed to detect genetic mutations associated with peroxisomal disorders, including PBD 8B.

Biochemical Testing Recommended first-tier biochemical testing for peroxisomal disorders includes analyzing very long-chain fatty acids (VLCFAs) using the POX / Fatty Acid Profile, Peroxisomal (C22-C26) test [5]. This test can help diagnose PBD 8B by detecting abnormal levels of VLCFAs in the blood.

Multiple-Gene Panel or Exome/Genome Approach Molecular testing can confirm biochemical findings and identify the specific genetic defect associated with PBD 8B, usually utilizing a multiple-gene panel or exome/genome approach [7]. This comprehensive testing strategy can provide a definitive diagnosis of PBD 8B.

Clinical Presentation-Based Testing The selection of laboratory studies for diagnosing peroxisomal disorders is based on the clinical presentation [4]. A combination of biochemical and molecular tests may be necessary to confirm the diagnosis of PBD 8B.

In summary, diagnostic tests for Peroxisome biogenesis disorder 8B include:

• Clinical Molecular Genetics Test
• Biochemical testing (POX / Fatty Acid Profile, Peroxisomal (C22-C26))
• Multiple-Gene Panel or Exome/Genome Approach
• Clinical presentation-based testing

These tests can help identify the genetic mutations and biochemical abnormalities associated with PBD 8B, leading to an accurate diagnosis.

References:

[1] Not provided in context. [2] Context #2 [4] Context #4 [5] Context #5 [7] Context #7

Treatment Options for Peroxisome Biogenesis Disorder (PBD)

Peroxisome biogenesis disorders, including Zellweger spectrum disorders (ZSD), are rare genetic conditions that affect the functioning of peroxisomes in cells. While there is currently no cure for PBD, treatment options are available to manage symptoms and improve quality of life.

Cholic Acid Therapy

One of the most effective treatments for PBD-ZSD is cholic acid therapy. Cholic acid is a bile acid that helps reduce toxic bile acid intermediates in the body, which can cause liver damage and other complications [7]. Studies have shown that cholic acid therapy can improve liver chemistries and reduce transaminase levels in patients with PBD-ZSD [4].

Adjunctive Treatment

Cholic acid is also approved by the FDA for adjunctive treatment of peroxisomal disorders, including Zellweger spectrum disorders. This means that it can be used in combination with other treatments to manage symptoms and improve outcomes [1].

Multidisciplinary Management

Management of PBD is multidisciplinary and symptomatic, involving a team of healthcare professionals, including hepatologists, neurologists, and geneticists. Treatment plans are tailored to individual patients based on their specific needs and symptoms [2].

Orphan Drugs

Peroxisome biogenesis disorders are rare conditions that benefit from treatment with orphan drugs. Utilization of known compounds, some of which are FDA-approved, can help manage symptoms and improve quality of life for patients with PBD [6].

References:

[1] Nov 30, 2022 — In March 2015, cholic acid (Cholbam) was approved by the FDA for adjunctive treatment of peroxisomal disorders, including Zellweger spectrum ...

[2] by C Argyriou · 2016 · Cited by 92 — 6. Management. There are no curative therapies for PBD. Management is multidisciplinary, symptomatic, and based on surveillance of the multiple ...

[4] 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 ...

[6] Peroxisome biogenesis disorders are rare, and thus benefit from treatment with orphan drugs. Utilization of known compounds, some of which are FDA approved ...

[7] by GM Enns · 2021 · Cited by 10 — Cholic acid (CA) therapy has demonstrated treatment efficacy in patients with PBD-ZSD, including decreased toxic bile acid intermediates, transaminase levels, ...

Peroxisome Biogenesis Disorder (PBD) Differential Diagnoses

Peroxisome biogenesis disorders, including the Zellweger spectrum disorder (ZSD), are a group of rare autosomal recessive diseases. When diagnosing PBDs, it's essential to consider other conditions that may present with similar symptoms.

Differential Diagnoses:

• Usher Syndrome I and II: These genetic disorders affect the eyes and ears, leading to hearing loss and vision impairment. While distinct from PBDs, they can be considered in differential diagnosis due to overlapping symptoms.
• Other Peroxisome Biogenesis Disorders (PBDs): This category includes various conditions caused by defects in peroxisomal biogenesis, such as Zellweger syndrome spectrum (ZSS) and rhizomelic chondrodysplasia punctata (RCDP). These disorders share similar biochemical features with PBD 8B.
• Single Enzyme Defects: Certain enzyme deficiencies can lead to elevated levels of Very Long Chain Fatty Acids (VLCFA), which is a hallmark of PBDs. However, these conditions are distinct from PBD 8B and require separate consideration.

Key Considerations:

When differentiating PBD 8B from other conditions, it's crucial to consider the following factors:

• Biochemical Features: Elevated levels of VLCFA and specific enzyme deficiencies can help distinguish PBDs from other disorders.
• Clinical Presentation: The severity and progression of symptoms, such as neurological defects and sensory loss, can aid in differential diagnosis.

References:

• [4] - The main differential diagnoses include Usher syndrome I and II, other PBD disorders (see these terms), single enzyme defects in peroxisome fatty acid beta-oxidation.
• [8] - The peroxisome biogenesis disorders are a heterogeneous group of rare autosomal recessive diseases. The unifying, underlying defect is the failure to form functional peroxisomes.

Note: The information provided above is based on the search results and context provided.