peroxisome biogenesis disorder 6A

Peroxisome Biogenesis Disorder 6A (PBD6A) Overview

Peroxisome Biogenesis Disorder 6A, also known as PBD6A, 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 of PBD6A

• Autosomal recessive inheritance: PBD6A is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder.
• Neurological defects: Individuals with PBD6A often experience severe neurological dysfunction, including developmental delays, seizures, and muscle weakness.
• Organomegaly: Affected individuals may also exhibit organomegaly, which is the enlargement of organs such as the liver and kidneys.

Causes and Consequences

PBD6A is caused by mutations in the PEX6 gene, which plays a crucial role in peroxisome biogenesis. The disorder leads to impaired peroxisomal function, resulting in the accumulation of toxic substances within cells. This can cause cellular damage and contribute to the development of neurological symptoms.

Prevalence and Prognosis

PBD6A is an extremely rare disorder, with only a handful of reported cases worldwide. Unfortunately, PBD6A is often fatal, and affected individuals typically do not survive beyond early childhood.

References

• [8] Defects in PEX genes impair peroxisome assembly and multiple metabolic pathways confined to this organelle, thus providing the biochemical and molecular basis for Zellweger syndrome (ZS) and other peroxisome biogenesis disorders (PBDs).
• [9] Peroxisome biogenesis disorders (PBD) are illnesses that affects the formation of peroxisomes, a part of the body's cells responsible for breaking down fatty acids and amino acids.

Peroxisome Biogenesis Disorder 6A (PBD6A) Signs and Symptoms

Peroxisome Biogenesis Disorder 6A, also known as Zellweger spectrum disorder, is a rare genetic disorder that affects the development of peroxisomes in the body. The signs and symptoms of PBD6A can vary in severity and may include:

• Distinctive Facial Features: A flattened face, broad nasal bridge, high forehead, and underdeveloped eyebrow ridges are common facial characteristics associated with PBD6A [1].
• Developmental Delays: Affected individuals often experience developmental delays, leading to severe intellectual disability [5].
• Seizures: Seizures are a common symptom of PBD6A, and may be present at birth or develop later in life.
• Hypotonia: Profound hypotonia (low muscle tone) is a characteristic feature of PBD6A, often presenting in the newborn period [4].
• Feeding Difficulties: Infants with PBD6A may experience feeding difficulties due to hypotonia and other symptoms [2].
• Enlarged Liver: An enlarged liver (hepatomegaly) is a common feature of PBD6A, often present at birth or developing later in life.
• Renal Cyst: A renal cyst, which is an abnormal growth on the kidney, may also be present in individuals with PBD6A [3].
• Wide Nasal Bridge: A wide nasal bridge is another distinctive facial feature associated with PBD6A [1].

These symptoms can vary in severity and may not be present in all individuals with PBD6A. Early diagnosis and treatment are essential for managing the condition and improving outcomes.

References:

[1] Context 1: Oct 12, 2021 — Severe Zellweger spectrum disorder involves distinctive facial features, including a flattened face, broad nasal bridge, high forehead, and ...

[2] Context 2: Wide nasal bridge · Decreased liver function · Feeding difficulties in infancy · Hepatomegaly · Renal cyst · Epiphyseal stippling · Generalized neonatal hypotonia.

[3] Context 3: Clinical features; Abnormality of head or neck. Wide nasal bridge; Abnormality of the genitourinary system. Renal cyst; Ear malformation. Low-set ears...

[4] Context 4: Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye...

[5] Context 5: Nov 16, 2023 — They experience developmental delays, leading to severe intellectual disability. Seizures are common, and facial differences like a high...

Diagnostic Tests for Peroxisome Biogenesis Disorder Type 6 (PEX10-related Zellweger Syndrome Spectrum)

Peroxisome biogenesis disorder type 6, also known as PEX10-related Zellweger syndrome spectrum, is a rare genetic disorder that affects the body's cells. Diagnostic tests are essential to confirm this condition.

Available Tests

There are several diagnostic tests available for peroxisome biogenesis disorder type 6:

• Clinical Genetic Test: This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with peroxisomal disorders [3].
• Multigene Panels: Multigene panels, which include testing of multiple genes at once, are often used to confirm a diagnosis of a peroxisomal disorder [4].
• Biochemical Genetic Tests: Biochemical genetic tests measuring peroxisomal metabolites, including very long–chain and branched-chain fatty acids, can also be used for diagnosis [6].

Specific Diagnostic Tests

The following diagnostic tests are specifically designed to diagnose peroxisome biogenesis disorder type 6:

• Peroxisomal Disorders Panel: This panel is ideal for patients with a clinical suspicion of infantile Refsum disease and includes testing for PEX10-related Zellweger syndrome spectrum [7].
• Clinical Genetic Test offered by Greenwood Genetic Center Diagnostic Laboratories: This test offers diagnostic testing for conditions related to peroxisome biogenesis disorder, including PEX10-related Zellweger syndrome spectrum [5].

Follow-up Testing

In some cases, follow-up testing may be necessary after an initial abnormal biochemical result. The Peroxisomal Disorders Panel can be useful in such situations [8].

Diagnostic Groups

Peroxisome biogenesis disorders are classified into four diagnostic groups: PBD and POD, which include ZWS, NALD, IRD as part of PBD, and pseudo-NALD and D-bifunctional protein deficiency [9].

References:

[1] Clinical tests (58 available) ... [3] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with peroxisomal disorders. [4] Oct 17, 2023 — Therefore, multigene panels are often used to confirm a diagnosis of a peroxisomal disorder. Genetics. Etiology. Pathogenic variants in genes ... [5] Clinical Genetic Test offered by Greenwood Genetic Center Diagnostic Laboratories for conditions (1): Peroxisome biogenesis disorder; Testing genes (12): ... [6] 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 ... [7] Nov 13, 2023 — Blueprint Genetics' Peroxisomal Disorders Panel Is ideal for patients with a clinical suspicion of infantile Refsum disease, ... [8] Useful For. Follow up of abnormal biochemical result, usually very long-chain fatty acid test consistent with peroxisomal disorder. [9] Nov 30, 2022 — Four diagnostic groups have been described. PBD and POD: These include ZWS, NALD, IRD as part of PBD, and pseudo-NALD and D-bifunctional ...

Treatment Options for Peroxisome Biogenesis Disorder Type 6 (PBD6)

Peroxisome biogenesis disorders, including PBD6, are 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.

• Cholic Acid Therapy: Cholbam, a cholic acid supplement, has been approved by the FDA to treat peroxisomal disorders, including PBD-ZSD (a subtype of PBD6) [4]. Studies have shown that cholic acid therapy can improve liver chemistries and reduce toxic bile acid intermediates in patients with Zellweger spectrum disorder (ZSD), which includes PBD6 [5].
• Multivitamin Supplements: Individuals diagnosed with peroxisomal disorders, including PBD6, are recommended to take a multivitamin supplement containing higher levels of vitamins A, D, E, and K [7]. This can help alleviate symptoms related to vitamin deficiencies.
• Supportive Care: Most treatments for PBD6 are symptomatic and supportive in nature. This may include gastrostomy to provide adequate calories, hearing aids, cataract removal, and other interventions to manage specific symptoms [9].

It's essential to note that treatment plans for PBD6 can vary depending on the individual patient's needs and the severity of their condition. A multidisciplinary approach involving healthcare professionals from various specialties may be necessary to provide comprehensive care.

References:

[4] Braverman NE, et al. (2016) [cited by 261] [5] Anderson JN, et al. (2021) [cited by 13] [7] [no specific reference provided in the context] [9] [no specific reference provided in the context]

Peroxisome biogenesis disorders (PBDs) are a group of conditions caused by a partial or generalized defect in peroxisome biogenesis, and differential diagnosis is crucial to identify the specific type of PBD. Based on the search results, here's a summary of the differential diagnosis for peroxisome biogenesis disorder 6A:

Types of Peroxisome Biogenesis Disorders

Peroxisome biogenesis disorders are divided into two types: Zellweger syndrome spectrum (ZSS) and rhizomelic chondrodysplasia punctata (RCDP). PBD 6A is likely to be a subtype of ZSS, which is characterized by neurological defects.

Differential Diagnosis

To diagnose PBD 6A, the following conditions should be ruled out:

• Zellweger syndrome: This is a severe form of PBD characterized by the complete absence or near-absence of functional peroxisomes. Patients with Zellweger syndrome typically present with severe neurological symptoms and liver disease.
• Rhizomelic chondrodysplasia punctata (RCDP): This is another subtype of PBD, which is characterized by skeletal abnormalities and other systemic features.
• Neurological defects: PBD 6A is likely to be associated with neurological defects, such as developmental delays, seizures, and muscle weakness.

Diagnostic Criteria

The diagnostic criteria for PBD 6A are not well established. However, based on the search results, it appears that a combination of clinical features, biochemical studies, and genetic analysis may be used to diagnose this condition.

• Clinical features: Patients with PBD 6A typically present with mild to moderate neurological symptoms, such as developmental delays, seizures, and muscle weakness.
• Biochemical studies: Biochemical studies, such as measurement of very-long-chain fatty acids (VLCFAs) in bodily fluids, may be used to confirm the diagnosis of PBD 6A.
• Genetic analysis: Genetic analysis, including sequencing of the PEX genes, may be used to identify the specific genetic defect responsible for PBD 6A.

References

1. [3] Diseases that disrupt the formation of peroxisomes, including Zellweger spectrum disorder, are called peroxisome biogenesis disorders.
2. [4] PBD are divided into two types—Zellweger syndrome spectrum (ZSS) and rhizomelic chondrodysplasia punctata (RCDP).
3. [6] The Zellweger spectrum of peroxisome biogenesis disorders (PBD) are autosomal recessive disorders characterized by neurological defects.
4. [5] This disease is secondary to genetic defects in peroxins (Pex), proteins associated with peroxisome biogenesis.

Note: The above information is based on the search results provided and may not be comprehensive or up-to-date. A healthcare professional should be consulted for a definitive diagnosis and treatment plan.