Peroxisome biogenesis disorder 5B

Peroxisome Biogenesis Disorder 5B (PBD5B): A Rare Genetic Condition

Peroxisome biogenesis disorder 5B, also known as PBD5B, is a rare genetic condition that affects the formation of functional peroxisomes in cells. Peroxisomes are organelles responsible for breaking down fatty acids and amino acids.

Clinical Features:

Individuals with PBD5B may exhibit a range of clinical features, including:

• Neonatal Adrenoleukodystrophy (NALD) and Infantile Refsum Disease (IRD): These are milder forms of the condition, characterized by developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal degeneration, and multiple organ dysfunction [11].
• Variable Clinical Course: The clinical course of patients with PBD5B can vary significantly, making diagnosis and management challenging.
• Sensorineural Hearing Loss: Many individuals with PBD5B experience sensorineural hearing loss, which can range from mild to severe.

Genetic Basis:

PBD5B is caused by mutations in the PEX2 gene on chromosome 8q21. These mutations impair peroxisome assembly and multiple metabolic pathways confined to this organelle [6].

Disease Definition:

Peroxisome biogenesis disorders, including PBD5B, are a group of autosomal recessive disorders affecting the formation of functional peroxisomes. This condition is characterized by sensorineural hearing loss, pigmentary retinal degeneration, multiple organ dysfunction, and psychomotor impairment [3].

References:

• [11] The overlapping phenotypes of NALD and IRD represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders.
• [6] Defects in PEX genes impair peroxisome assembly and multiple metabolic pathways confined to this organelle, thus providing the biochemical and molecular basis for these disorders.
• [3] Peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD-ZSS) is a group of autosomal recessive disorders affecting the formation of functional peroxisomes...

Common Signs and Symptoms of Peroxisome Biogenesis Disorder 5B (PBD5B)

Peroxisome biogenesis disorders, including PBD5B, are a group of rare genetic conditions that affect the functioning of peroxisomes in cells. The signs and symptoms of PBD5B can vary in severity and range from mild to severe.

Common Features:

• Developmental Delays: Individuals with PBD5B often experience significant developmental delays, which can lead to intellectual disability [1].
• Neurological Deficits: Neurological problems are common, including seizures, loss of muscle tone (hypotonia), and peripheral neuropathy [3][7].
• Hearing and Vision Problems: Hearing and vision impairments are also frequently observed in individuals with PBD5B [2][4].
• Liver Dysfunction: Liver dysfunction is a common finding in affected patients [3].

Other Possible Symptoms:

• Facial Differences: Some individuals may have facial differences, such as a high forehead or other distinctive features [4].
• Kidney Abnormalities: Kidney abnormalities can also occur in some cases [3].
• Ataxia and Peripheral Neuropathy: Ataxia (loss of coordination) and peripheral neuropathy (nerve damage) are possible symptoms [7].

Age at Presentation:

The severity and range of signs and symptoms vary according to the age at presentation. In general, individuals with severe PBD5B tend to have more pronounced symptoms from birth, which worsen over time [5].

Based on the provided context, it appears that there are several diagnostic tests available for peroxisome biogenesis disorder 5B (PBD-ZSD). Here's a summary of the relevant information:

• Genetic testing: The genetic test helps identify PBD-ZSD, a rare autosomal recessive disorder [4]. This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with peroxisomal disorders [2].
• Multigene panels: Multigene panels are often used to confirm a diagnosis of a peroxisomal disorder, including PBD-ZSD [7].
• Biochemical genetic tests: The current diagnostic approach relies heavily on biochemical genetic tests measuring peroxisomal metabolites, including very long–chain and branched-chain fatty acids [5].

It's worth noting that the clinical course of patients with PBD-ZSD can be variable, and may include developmental delay, hypotonia, and other symptoms [1]. Therefore, a comprehensive diagnostic approach may involve a combination of genetic testing, biochemical analysis, and clinical evaluation.

References:

[1] 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. [Context 1] [2] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with peroxisomal disorders. [Context 2] [4] The genetic test helps identify peroxisome biogenesis disorder-Zellweger spectrum disorder (PBD-ZSD), a rare autosomal recessive disorder. [Context 4] [5] by I De Biase · 2020 · Cited by 23 — The current diagnostic approach relies heavily on biochemical genetic tests measuring peroxisomal metabolites, including very long–chain and branched-chain ... [Context 5] [7] Oct 17, 2023 — Therefore, multigene panels are often used to confirm a diagnosis of a peroxisomal disorder. Genetics. Etiology. Pathogenic variants in genes ... [Context 7]

Treatment Options for Peroxisome Biogenesis Disorder 5B

Peroxisome biogenesis disorders (PBDs) are a group of rare genetic conditions that affect the formation and function of peroxisomes, which are organelles found in cells. PBD-5B is one such disorder.

While there is currently no cure for PBD-5B, treatment options are available to manage symptoms and improve quality of life. According to recent studies [4][9], symptomatic treatment is the mainstay of management for PBDs, including PBD-5B.

Cholic Acid (Cholbam) Therapy

One of the most promising treatments for PBD-5B is cholic acid (Cholbam), a medication approved by the FDA in 2015 [1]. Cholbam has been shown to improve liver chemistries and reduce toxic bile acids in patients with Zellweger spectrum disorders, including PBD-5B [5].

Other Treatment Options

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

• Anti-epileptic drugs to manage seizures
• Dietary modifications and supplements to support overall health
• Multidisciplinary care involving specialists in pediatrics, gastroenterology, and neurology

Importance of Early Diagnosis and Management

Early diagnosis and management are crucial for improving outcomes in patients with PBD-5B. A multidisciplinary approach that involves a team of healthcare professionals can help manage symptoms, prevent complications, and improve quality of life.

References:

[1] FDA approval of Cholbam for adjunctive treatment of peroxisomal disorders (2015)

[4] Braverman NE et al. (2016) Recent advances in the diagnosis and management of peroxisome biogenesis disorders

[5] Anderson JN et al. (2021) Safety and efficacy of cholic acid therapy in patients with Zellweger spectrum disorders

[9] NORD rare disease drug development ad. on Peroxisome Biogenesis Disorders

Peroxisome biogenesis disorder 5b (PBD5B) encompasses neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), both milder forms of peroxisomal disorders. To establish a differential diagnosis for PBD5B, consider the following conditions:

• Zellweger spectrum disorder (ZSD): A group of autosomal recessive disorders affecting peroxisome biogenesis, characterized by sensorineural hearing loss, pigmentary retinal dystrophy, and other systemic features. ZSD is a milder form of PBD5B.
• Rhizomelic chondrodysplasia punctata (RCDP): A rare genetic disorder affecting peroxisome biogenesis, characterized by skeletal abnormalities, facial dysmorphism, and other systemic features. RCDP is another condition within the PBD spectrum.
• Neonatal adrenoleukodystrophy (NALD): A severe form of ZSD, characterized by adrenal insufficiency, leukodystrophy, and other systemic features.
• Infantile Refsum disease (IRD): A milder form of ZSD, characterized by retinitis pigmentosa, sensorineural hearing loss, and other systemic features.

When differentiating PBD5B from these conditions, consider the following key features:

• Age of onset: PBD5B typically presents in infancy or early childhood, whereas NALD and IRD present in the neonatal period.
• Clinical presentation: PBD5B is characterized by a milder clinical presentation compared to ZSD, with fewer systemic features and no adrenal insufficiency.
• Biochemical findings: Elevated levels of very-long-chain fatty acids (VLCFAs) are characteristic of all peroxisomal disorders, including PBD5B.

A comprehensive diagnostic evaluation, including biochemical analysis, imaging studies, and genetic testing, is essential to establish a differential diagnosis for PBD5B. Consultation with a specialist in medical genetics or a pediatrician experienced in the care of children with rare genetic disorders may be necessary to ensure accurate diagnosis and management.

References:

• [1] Peroxisome biogenesis disorder 5b is a condition that encompasses neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), both milder forms of peroxisomal disorders. (Source: #3)
• ZSD are inherited in an autosomal recessive pattern. ZSD are also known as peroxisome biogenesis disorders (PBDs) – a group of disorders characterized by the impaired formation of functional peroxisomes. (Source: #5)
• The Zellweger spectrum of peroxisome biogenesis disorders (PBD) are autosomal recessive disorders characterized by neurological defects (including sensorineural hearing loss), pigmentary retinal dystrophy, and other systemic features. (Source: #8)
• Peroxisome biogenesis disorders include Zellweger spectrum disorders (ZSDs) and rhizomelic chondrodysplasia punctata (RCDP). Single enzyme deficiencies can also be part of this group. (Source: #10)