peroxisome biogenesis disorder 11A

Peroxisome biogenesis disorder 11A, also known as Zellweger syndrome, is a rare and fatal genetic disorder that affects the formation of functional peroxisomes in cells.

Characteristics:

• Severe neurologic dysfunction
• Profound psychomotor retardation
• Hypotonia (low muscle tone)
• Craniofacial anomalies, including anteverted nares, depressed nasal bridge, high forehead, large face, and triangular face [1][2]
• Elevated circulating hepatic transaminase concentration [2]

Clinical Features:

• Abnormality of head or neck
• Anteverted nares
• Depressed nasal bridge
• High forehead
• Large face
• Triangular face
• Abnormality of metabolism

Symptoms:

• Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed [5]
• Characteristic craniofacial anomalies, eye abnormalities, and sensorineural hearing loss [3]

Peroxisome biogenesis disorder 11A is a part of the peroxisome biogenesis disorders (PBD) group, which are genetically heterogeneous with at least 14 distinct genetic groups [9]. It is characterized by severe neurologic dysfunction, profound psychomotor retardation, hypotonia, and craniofacial anomalies.

References: [1] - Context result 4 [2] - Context result 2 [3] - Context result 5 [4] - Not applicable (no relevant information) [5] - Context result 5 [6] - Not applicable (no relevant information) [7] - Not applicable (no relevant information) [8] - Context result 8 [9] - Context result 9

Peroxisomal Disorder 11A (Zellweger Syndrome) Signs and Symptoms

Peroxisomal disorder 11A, also known as Zellweger syndrome, is a rare genetic disorder that affects the development and function of peroxisomes in the body. The signs and symptoms of this condition can vary in severity and may include:

• Distinctive facial features: A flattened face, broad nasal bridge, high forehead, and triangular face shape are common characteristics of individuals with Zellweger syndrome [2].
• Abnormal metabolism: This disorder is characterized by impaired peroxisomal function, leading to abnormal metabolism and accumulation of toxic substances in the body [3].
• Hepatic dysfunction: Progressive liver dysfunction is a hallmark symptom of Zellweger syndrome, often resulting in elevated circulating hepatic transaminase concentration [4].
• Renal cysts: Multiple renal cysts can be present in individuals with this condition [5].
• Neurological issues: Seizures, developmental delay, feeding issues, and hypotonia (low muscle tone) are common neurological symptoms associated with Zellweger syndrome [6].
• Hearing and vision loss: Some individuals may experience hearing and vision loss due to the disorder's impact on peroxisomal function [7].
• Neonatal seizures: Seizures can occur in newborns with Zellweger syndrome, often accompanied by liver dysfunction and other symptoms [8].

It is essential to note that the severity and presentation of these signs and symptoms can vary significantly among individuals with peroxisomal disorder 11A.

Diagnostic Tests for Peroxisome Biogenesis Disorder 11A (PBD-ZSD)

Peroxisome biogenesis disorders, including PBD-ZSD, can be diagnosed through various genetic and biochemical tests. Here are some diagnostic tests used to confirm a diagnosis of PBD-ZSD:

• Multigene panels: These tests utilize next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with peroxisomal disorders (Source: [3]). The clinical utility of this panel is estimated to be >85% for the main peroxisome biogenesis disorders (Source: [5]).
• Biochemical genetic tests: These tests measure peroxisomal metabolites, including very long-chain and branched-chain fatty acids, in blood and urine (Source: [8]). DNA testing is also possible for all of the disorders, but is more challenging for PBD-ZSD.
• Genetic testing: Genetic testing can be used to confirm a diagnosis of PBD-ZSD by identifying mutations in PEX genes responsible for normal peroxisome assembly and functions (Source: [12]).

Clinical Genetic Tests

The Greenwood Genetic Center Diagnostic Laboratories offer a clinical genetic test for conditions, including Peroxisome biogenesis disorder 11A (Zellweger) (Source: [2]). This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with peroxisomal disorders.

References

[1] Clinical resource with information about Peroxisome biogenesis disorder 11A (Zellweger) and its clinical features, PEX13, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB. [2] Clinical Genetic Test offered by Greenwood Genetic Center Diagnostic Laboratories for conditions (1): Peroxisome biogenesis disorder; Testing genes (12): ... [3] Oct 17, 2023 — Therefore, multigene panels are often used to confirm a diagnosis of a peroxisomal disorder. Genetics. Etiology. Pathogenic variants in genes ... [4] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with peroxisomal disorders. [5] Nov 13, 2023 — The clinical utility of this panel is estimated to be >85% for the main peroxisome biogenesis disorders. The strengths of this test include: CAP ... [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 30, 2022 — Four diagnostic approaches are used to diagnose PBD-ZSD: clinical evaluation, imaging studies, biochemical testing, and molecular analysis. [8] 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 ... [9] Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. [10] Abstract. Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. [11] Peroxisomal disorders are a clinically and genetically heterogeneous group of diseases caused by defects in peroxisomal biogenesis or function, usually impairing several metabolic pathways. Peroxisomal disorders are rare; however, the incidence may be underestimated due to the broad spectrum of clin … [12] peroxisome biogenesis disorder 11A (Zellweger) ... (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH). [13] Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes. OMIM focuses on the relationship between phenotype and genotype.

Treatment Options for Peroxisome Biogenesis Disorder 11A

Peroxisome biogenesis disorder 11A, also known as Zellweger syndrome, is a rare genetic disorder that affects the formation and function of peroxisomes in the body. While there is no cure for this condition, various treatment options are available to manage its symptoms and improve quality of life.

Cholic Acid Therapy

One of the most effective treatments for Zellweger syndrome is cholic acid therapy. Cholic acid is a bile acid that helps to reduce toxic bile acid intermediates in the body, which can cause liver damage and other complications [2]. Studies have shown that cholic acid therapy can improve liver chemistries and reduce the risk of liver disease in patients with Zellweger syndrome [5].

Adjunctive Treatment

Cholic acid is also indicated 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 quality of life [4]. In patients who exhibit severe liver disease or other complications, cholic acid therapy may be recommended as an adjunctive treatment.

Other Treatment Options

While there is limited research on the effectiveness of other treatments for Zellweger syndrome, some studies suggest that pharmacologic therapies such as Lorenzo's oil, docosohexanoic acid, and batyl alcohol may have a beneficial effect on symptoms [7]. Additionally, bisphosphonate medications have been used to treat bone disease in patients with Zellweger syndrome, with reported success [9].

Autophagy Inhibitors

Recent studies have also explored the use of autophagy inhibitors as a potential treatment for peroxisome biogenesis disorders. Autophagy inhibitors have been shown to improve peroxisomal function by stabilizing the presence of mature peroxisomes in cells [8]. However, more research is needed to fully understand their effectiveness and potential benefits.

Conclusion

While there is no cure for Zellweger syndrome, various treatment options are available to manage its symptoms and improve quality of life. Cholic acid therapy remains one of the most effective treatments, but other options such as adjunctive treatment, pharmacologic therapies, bisphosphonate medications, and autophagy inhibitors may also be considered on a case-by-case basis.

References:

[2] - [5], [7], [8], [9]

Differential Diagnosis of Peroxisome Biogenesis Disorder (PBD) 11A

Peroxisome biogenesis disorders (PBDs) are a group of conditions caused by defects in the formation of functional peroxisomes. PBD 11A is one such disorder, and its differential diagnosis involves identifying other conditions that may present with similar symptoms.

Similar Conditions:

• Usher syndrome I and II: These genetic disorders also affect the nervous system and can cause hearing loss, visual impairment, and balance problems.
• Other PBDs: Disorders like Zellweger spectrum disorder (ZSD), rhizomelic chondrodysplasia punctata (RCDP), and neonatal adrenoleukodystrophy (NALD) may also be considered in the differential diagnosis of PBD 11A.
• Single enzyme defects in peroxisome fatty acid beta-oxidation: Defects in enzymes involved in fatty acid metabolism can lead to similar symptoms, such as hearing loss and visual impairment.

Key Features:

• Sensorineural hearing loss: A common feature of PBDs, including PBD 11A.
• Pigmentary retinopathy: Some PBDs may present with changes in the retina, which can lead to vision problems.
• Neurological defects: Many PBDs are associated with neurological symptoms, such as seizures and developmental delays.

References:

• [1] Peroxisome biogenesis disorders (PBD) are a group of conditions caused by defects in the formation of functional peroxisomes. [2]
• 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. [6]
• Zellweger spectrum disorder is a type of PBD that can cause sensorineural hearing loss, pigmentary retinopathy, and neurological defects. [3]

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