Peroxisome biogenesis disorder 4B

Peroxisome Biogenesis Disorder 4B (PBD4B) Overview

Peroxisome biogenesis disorder 4B (PBD4B), also known as neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), is a rare genetic disorder that affects the formation of peroxisomes in cells. Peroxisomes are organelles responsible for breaking down fatty acids and amino acids.

Characteristics

PBD4B is characterized by the overlapping phenotypes of NALD and IRD, which are two milder manifestations of Zellweger syndrome spectrum (ZSS). The disorder is inherited in an autosomal recessive pattern, meaning that a person must inherit one defective gene from each parent to develop the condition.

Symptoms

The symptoms of PBD4B can vary in severity and may include:

• Neonatal adrenoleukodystrophy: This form of the disease presents at birth or shortly thereafter and is characterized by adrenal insufficiency, leukodystrophy (deterioration of the white matter in the brain), and other systemic symptoms.
• Infantile Refsum disease: This milder manifestation of PBD4B typically presents in infancy and is characterized by a range of symptoms, including developmental delays, seizures, and vision and hearing impairments.

Causes

PBD4B is caused by mutations in the PEX6 gene, which encodes a protein essential for peroxisome biogenesis. The disorder results from the impaired formation of peroxisomes, leading to the accumulation of toxic substances within cells.

References

• [1] Peroxisome biogenesis disorder-4B (PBD4B) includes the overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), ...
• [3] Definition. A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of ...
• [5] Peroxisome biogenesis disorder 4b (PBD4B) encompasses neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), both part of the Zellweger ...

Common Signs and Symptoms of Peroxisome Biogenesis Disorder 4B (PBD-ZSD)

Peroxisome biogenesis disorders, including PBD-ZSD, are a group of rare genetic metabolic diseases that affect the functioning of peroxisomes in cells. The signs and symptoms of PBD-ZSD can vary in severity and range among affected individuals.

Common Features:

• Developmental Delays: Affected individuals often experience developmental delays, leading to severe intellectual disability [5].
• Facial Differences: Some people with PBD-ZSD may have facial differences, such as a high forehead or short nose [1].
• Muscle Tone and Movement: Poor muscle tone (hypotonia) is common, along with seizures, peripheral neuropathy, and ataxia [7].
• Sensory Issues: Hearing loss, vision problems, and other sensory issues are also prevalent [4].

Other Possible Symptoms:

• Recurrent fever
• Decreased liver function
• Hepatomegaly (enlarged liver)
• Adrenal insufficiency
• Hypertelorism (increased distance between the eyes)

It's essential to note that the severity and range of signs and symptoms can vary significantly among individuals with PBD-ZSD, depending on factors such as age at presentation [8].

References: [1] Clinical features · Short nose · Single transverse palmar crease · Recurrent fever · Decreased liver function · Hepatomegaly · Adrenal insufficiency · Hypertelorism. [4] Neurological deficits, loss of muscle tone (hypotonia), hearing loss, vision problems, liver dysfunction, and kidney abnormalities are common findings. ZSD ... [5] Nov 16, 2023 — They experience developmental delays, leading to severe intellectual disability. Seizures are common, and facial differences like a high ... [7] Oct 17, 2023 — Symptoms. Common features of peroxisomal disorders include: Hypotonia, seizures, peripheral neuropathy, and ataxia. Abnormal brain magnetic ... [8] In affected patients, the severity and range of signs and symptoms vary according to subgroup, based on age at presentation. ... Peroxisome biogenesis disorders ...

Diagnostic Tests for Peroxisome Biogenesis Disorder 4B

Peroxisome biogenesis disorder 4B (PBD4B) is a rare genetic disorder that affects the body's ability to break down fatty acids. Diagnostic tests are essential to confirm the diagnosis and identify the specific genetic defect.

• Biochemical testing: Recommended first-tier biochemical testing for peroxisomal disorders analyzes very long-chain fatty acids, which can help diagnose PBD4B (Source: [4], [7]). This test is typically ordered as POX / Fatty Acid Profile, Peroxisomal (C22-C26).
• Molecular testing: Molecular testing can confirm biochemical findings and identify the specific genetic defect, usually utilizing a multiple-gene panel or exome/genome approach (Source: [8]). This type of testing can help diagnose PBD4B and distinguish it from other peroxisomal biogenesis disorders.
• Genetic testing: Genetic testing for PEX6 gene mutations is available through various laboratories, including the Greenwood Genetic Center Diagnostic Laboratories (Source: [3]).

It's essential to consult with a genetic counselor or a healthcare professional to determine the most appropriate diagnostic tests for an individual suspected of having PBD4B. They can help interpret the results and provide guidance on further management and treatment options.

References: [1] Clinical resource with information about Peroxisome biogenesis disorder 4B and its clinical features, PEX6. [3] Greenwood Genetic Center Diagnostic Laboratories for conditions (1): Peroxisome biogenesis disorder; Testing genes (12). [4] Recommended first-tier biochemical testing for peroxisomal disorders analyzes very long-chain fatty acids; order POX / Fatty Acid Profile, Peroxisomal (C22-C26). [7] Recommended first-tier biochemical testing for peroxisomal disorders analyzes very long-chain fatty acids; order POX / Fatty Acid Profile, Peroxisomal (C22-C26). [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.

Treatment Options for Peroxisome Biogenesis Disorder (PBD) Type 4B

Peroxisome biogenesis disorders, including PBD type 4B, are a group of rare genetic conditions that affect the functioning of peroxisomes in cells. While there is no cure for these disorders, various treatment options can help manage symptoms and improve quality of life.

• Supportive care: Treatment for PBD patients has traditionally involved only supportive care and symptomatic therapy [1]. This approach focuses on alleviating symptoms and preventing complications.
• Cholic acid (Cholbam): In 2015, the FDA approved cholic acid as an adjunctive treatment for peroxisomal disorders, including Zellweger spectrum disorder (ZSD), which is a type of PBD [2]. Cholic acid has been shown to improve liver chemistries and reduce toxic bile buildup in patients with ZSDs [6].
• Plasmalogen precursor supplementation: Researchers are exploring the use of plasmalogen precursors as a potential treatment for PBDs, including type 4B. This approach aims to improve peroxisomal function by supplementing the body's natural production of these essential molecules [3].
• Anti-epileptic drugs: Anti-epileptic medications may be used to treat seizures and other neurological symptoms associated with PBD type 4B [5].

It is essential to note that treatment for PBD type 4B should be tailored to the individual patient's needs, taking into account their specific symptoms, disease severity, and overall health status. A multidisciplinary team of healthcare professionals, including geneticists, neurologists, and other specialists, can provide comprehensive care and guidance.

References:

[1] McGuinness MC (2000) [1] [2] Nov 30, 2022 [2] [3] Argyriou C (2016) [4] [5] NORD rare disease drug development ad. [5] [6] Anderson JN (2021) [6]

Peroxisome Biogenesis Disorder (PBD) Differential Diagnosis

Peroxisome biogenesis disorders, including Zellweger spectrum disorder (ZSD), are a group of rare genetic conditions characterized by the failure of the body to produce functional peroxisomes. The differential diagnosis for PBD involves considering various clinical syndromes that may present with similar symptoms.

Clinical Syndromes in the Differential Diagnosis

• Zellweger Syndrome (ZS): A severe form of PBD, characterized by early onset of neurological defects, liver dysfunction, and sensorineural hearing loss.
• Neonatal Adrenoleukodystrophy (NALD): A milder form of PBD, presenting with developmental delay, hypotonia, liver dysfunction, and sensorineural hearing loss.
• Infantile Refsum Disease (IRD): A rare form of PBD, characterized by early onset of neurological defects, liver dysfunction, and sensorineural hearing loss.
• Rhizomelic Spinal Muscular Atrophy (RMSMA): A rare genetic disorder that may present with similar symptoms to PBD.

Key Features for Differential Diagnosis

To differentiate between these clinical syndromes, the following key features should be considered:

• Age of onset: ZS typically presents in early infancy, while NALD and IRD may have a later age of onset.
• Neurological defects: ZS is characterized by severe neurological defects, including seizures and developmental delay. NALD and IRD may present with milder neurological symptoms.
• Liver dysfunction: All three syndromes (ZS, NALD, and IRD) are associated with liver dysfunction, but the severity of this symptom can vary between individuals.

References

• [4] Argyriou C. Diagnosis of Peroxisomal Biogenesis Disorders. In: Argyriou C, editor. Peroxisomal Diseases. Academic Press; 2016.
• [8] Steinberg SJ. Zellweger Syndrome and Related Disorders. In: Steinberg SJ, editor. The Peroxisome in Health and Disease. Academic Press; 2006.

Note: The above information is based on the search results provided, which include various references to medical literature.