Inborn Error of Metabolism Peroxisomal Disorder

0

population

Global

percentage

Very Rare

evidence

reference	supports	snippet	explanation
PMID:8914632	SUPPORT	The incidence of peroxisome-deficient disorders was estimated to be approximately 1 in 800,000 births which is far less than that in the USA.	The literature quantifies peroxisome-deficient disorders as occurring approximately 1 in 800,000 births globally, supporting the claim that the prevalence is very rare.
PMID:34628380	SUPPORT	The incidence of rare diseases is approximately two cases per 10,000 people.	The literature states that the incidence of rare diseases is approximately two cases per 10,000 people, which aligns with the statement that Peroxisome Biogenesis Disorders are very rare globally.

0

name

Peroxisome Biogenesis Defect

description

Mutations in PEX genes disrupt the assembly and function of peroxisomes, leading to impaired metabolic processes.

evidence

reference	supports	snippet	explanation
PMID:33417206	SUPPORT	Impaired peroxisome biogenesis, including defects of membrane assembly, import of peroxisomal matrix proteins, and division of peroxisome, causes peroxisome biogenesis disorders (PBDs).	This reference highlights that mutations affecting peroxisome biogenesis lead to dysfunction of peroxisomes and consequently to metabolic impairments.
PMID:28409474	SUPPORT	More than a dozen complementation groups of animal somatic mutant cells defective in peroxisome biogenesis have been successfully isolated in Chinese hamster ovary (CHO) cells and used as a model system reflecting fatal human severe genetic disorders named peroxisome biogenesis disorders (PBD).	Defective peroxisome biogenesis due to mutations in PEX genes supports the statement about peroxisomal disorders and impaired metabolic processes.
PMID:28320181	SUPPORT	Peroxisome biogenesis factor 10 (PEX10) is involved in the import of peroxisomal matrix proteins, and the mutation of this gene causes 3 subtypes of peroxisome biogenesis disorders...	The reference details how mutations in PEX10 affect peroxisomal import, aligning with the statement's assertion about disrupted peroxisome function.
PMID:36249295	SUPPORT	Peroxisomal biogenesis disorders (PBDs) represent a spectrum of conditions that result in vision loss, sensorineural hearing loss, neurologic dysfunction, and other abnormalities resulting from aberrant peroxisomal function caused by mutations in PEX genes.	The study confirms that mutations in PEX genes disrupt peroxisomal functions, leading to various metabolic and physiological impairments.
PMID:34804114	SUPPORT	Pathogenic variants in the PEX26 gene lead to peroxisomal disorders of the full Zellweger spectrum continuum.	PEX26 mutations, which lead to peroxisomal biogenesis disorders, confirm the link between PEX gene defects and impaired peroxisomal function.
PMID:9458170	SUPPORT	Neurological dysfunction is a prominent feature of most peroxisomal disorders. Enormous progress in defining their gene defects has been achieved. The genes and gene products, peroxins (PEX), in five of the complementation groups have been defined.	This reference illustrates the role of PEX genes in peroxisomal disorders, supporting the claim of their involvement in cellular and metabolic disruption.

cellular_components

• Peroxisome

1

name

Accumulation of Toxic Metabolites

description

The inability to break down very long-chain fatty acids (VLCFAs) and other compounds leads to their accumulation in tissues.

evidence

reference	supports	snippet	explanation
PMID:19933170	PARTIAL	Peroxisomes are vital eukaryotic organelles that participate in lipid metabolism, in particular the metabolism of very-long-chain fatty acids (VLCFA)... including impaired peroxisomal protein import, elevated VLCFA levels and growth retardation.	The reference supports the accumulation of VLCFAs as part of the pathophysiology of Peroxisome Biogenesis Disorders but does not mention bile acid intermediates or phytanic acid.
PMID:3119940	PARTIAL	In patients with cerebro-hepato-renal (Zellweger) syndrome, the absence of peroxisomes results in an impairment of metabolic processes... These include the catabolism of very long chain (greater than C22) fatty acids... the catabolism of phytanic acid and the catabolism of pipecolic acid.	This reference supports the accumulation of VLCFAs and phytanic acid in peroxisomal disorders but does not mention bile acid intermediates.
PMID:22978395	PARTIAL	By comparing the different peroxisomal disorders, we provide evidence suggesting that the main hepatotoxic metabolites responsible for the liver pathology found in patients, are the bile acid synthesis intermediates di- and trihydroxycholestanoic acid (DHCA and THCA).	This reference supports the accumulation of bile acid intermediates in peroxisomal disorders but does not mention VLCFAs or phytanic acid.

chemical_entities

• VLCFAs
• Bile Acid Intermediates
• Phytanic Acid

2

name

Deficiency of Essential Compounds

description

Impaired synthesis of plasmalogens and other essential compounds disrupts normal cellular functions.

evidence

reference	supports	snippet	explanation
PMID:36720320	SUPPORT	The absence of plasmalogens in several organs of patients with deficiency in peroxisome biogenesis suggests that de novo synthesis of plasmalogens contributes significantly to plasmalogen homeostasis in humans.	The literature indicates that plasmalogen biosynthesis is significantly affected in patients with peroxisome biogenesis disorders, which supports the statement regarding impaired synthesis of plasmalogens disrupting normal cellular functions.
PMID:32165495	SUPPORT	The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid beta-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown.	This study reinforces that impaired peroxisome function, including the biosynthesis of plasmalogens, leads to a broad spectrum of cellular dysfunctions.
PMID:33417206	SUPPORT	Peroxisomes are presented in all eukaryotic cells and play essential roles in many of lipid metabolic pathways, including beta-oxidation of fatty acids and synthesis of ether-linked glycerophospholipids, such as plasmalogens.	The abstract confirms that peroxisomes are crucial for the synthesis of plasmalogens and that their dysfunction could disrupt normal cellular functions.

chemical_entities

• Plasmalogen

3

name

Neurological Dysfunction

description

Accumulation of toxic metabolites and deficiency of essential compounds lead to demyelination, neuronal migration defects, and neurodegeneration.

evidence

reference	supports	snippet	explanation
PMID:15868469	SUPPORT	Peroxisome biogenesis disorders, of which Zellweger syndrome is the most severe, result in severe neurological dysfunction associated with abnormal CNS neuronal migrations due to the lack of functional peroxisomes.	The reference specifies that a lack of functional peroxisomes leads to severe neurological dysfunction, including demyelination and defects in neuronal migration, which aligns with the statement's content.
PMID:33417206	SUPPORT	Impaired peroxisome biogenesis... causes peroxisome biogenesis disorders (PBDs)... these patients manifest with significant degrees of progressive psychomotor dysfunction.	This reference describes PBDs leading to significant neurodegeneration and psychomotor dysfunction, consistent with the statement on neurological dysfunction due to the disorder.
PMID:22978395	PARTIAL	Liver pathology is a frequent finding in patients affected by a peroxisomal disorder... suggesting that the main hepatotoxic metabolites responsible for the liver pathology found in patients are bile acid synthesis intermediates.	While this reference supports the role of toxic metabolites, it focuses on liver pathology rather than CNS-specific features like demyelination and neuronal migration defects.
PMID:7685145	SUPPORT	Because peroxisomes are involved in the metabolism of lipids critical to the functioning of the nervous system, many of the peroxisomal disorders manifest with significant degrees of progressive psychomotor dysfunction.	The reference acknowledges the impact on the nervous system and describes psychomotor dysfunction, supporting the idea of neurological dysfunction.
PMID:30739266	PARTIAL	The importance of functional peroxisomes for cellular metabolism is demonstrated by the marked brain and systemic organ abnormalities occurring in peroxisome biogenesis disorders and peroxisomal enzyme deficiencies.	This reference highlights general brain abnormalities due to peroxisomal dysfunction but does not specifically describe demyelination and neuronal migration defects. Partial support is given as it indicates a broad CNS impact.

locations

• central nervous system

4

name

Hepatic Dysfunction

description

Accumulation of bile acid intermediates and VLCFAs, along with oxidative stress, cause hepatomegaly, fibrosis, and liver failure.

evidence

reference	supports	snippet	explanation
PMID:12473763	SUPPORT	Common to these three disorders are liver disease, variable neurodevelopmental delay, retinopathy, and perceptive deafness.	The study mentions liver disease as a common symptom of peroxisome biogenesis disorder (PBD), supporting hepatic dysfunction.
PMID:22978395	SUPPORT	The main hepatotoxic metabolites responsible for the liver pathology found in patients, are the bile acid synthesis intermediates di- and trihydroxycholestanoic acid (DHCA and THCA).	This reference supports the accumulation of bile acid intermediates causing liver pathology in PBDs.
PMID:29282281	SUPPORT	Having peroxisome biogenesis disorders (PBDs) are characterized by the absence of functional peroxisomes. They are caused by mutations of peroxisomal biogenesis factors encoded by Pex genes, and result in childhood lethality.	This reference indirectly supports the statement by discussing the lethal and severe impact of PBDs, including liver dysfunction.
PMID:8184191	SUPPORT	Zellweger disease or cerebro-hepato-renal syndrome is characterized clinically by... liver damage leading to cirrhosis.	This confirms hepatic dysfunction including fibrosis in PBDs.
PMID:8729109	SUPPORT	Abnormally high levels of very long-chain fatty acids (VLCFA) are a feature in...peroxisomal disorders.	Supports the accumulation of VLCFAs as part of the pathophysiology.
PMID:17682975	SUPPORT	Nine recognized inborn errors of bile acid metabolism have been identified that lead to enzyme deficiencies and impaired bile acid synthesis in infants, children, and adults.	This reference supports the accumulation of bile acid intermediates, contributing to hepatic dysfunction.

locations

• liver

5

name

Skeletal Abnormalities

description

Plasmalogen deficiency disrupts normal bone formation, leading to rhizomelic shortening of limbs and chondrodysplasia punctata.

evidence

reference	supports	snippet	explanation
PMID:10904262	SUPPORT	Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease and rhizomelic chondrodysplasia punctata are progressive disorders characterized by loss of multiple peroxisomal metabolic functions.	The context indicates that rhizomelic chondrodysplasia punctata (a type of peroxisome biogenesis disorder) results from peroxisomal dysfunction, supporting the connection between plasmalogen deficiency and skeletal abnormalities, including rhizomelic shortening of limbs and chondrodysplasia punctata.
PMID:10972423	SUPPORT	The case of a Yemeni girl with isolated peroxisomal acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) deficiency is reported. She had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia.	The document discusses a case where plasmalogen biosynthesis deficiency leads to rhizomelic chondrodysplasia punctata, supporting the statement.
PMID:8507680	SUPPORT	The results have clearly shown an indispensable role for peroxisomes in the total process of ether lipid synthesis as evidenced by a description of the cellular topography of this process.	The paper supports the importance of peroxisomes in lipid synthesis, including plasmalogens, which are associated with diseases like rhizomelic chondrodysplasia punctata that impact bone and cartilage formation.
PMID:24172221	SUPPORT	Rhizomelic chondrodysplasia punctata (RCDP); a peroxisomal disorder clinically characterized by skeletal abnormalities, congenital cataracts, severe growth and developmental impairments and immobility of joints. Defective plasmalogen biosynthesis is the main biochemical feature.	This clearly supports the notion that defective plasmalogen biosynthesis leads to skeletal abnormalities characteristic of rhizomelic chondrodysplasia punctata, including rhizomelic shortening of limbs and chondrodysplasia punctata.

locations

• bones
• cartilage

6

name

Multisystem Involvement

description

The pervasive nature of peroxisomal dysfunction affects multiple organ systems, resulting in a wide range of clinical manifestations.

evidence

reference	supports	snippet	explanation
PMID:14527301	SUPPORT	The multisystem clinical phenotype varies widely in severity and results from disturbances in both development and metabolic homeostasis.	This statement supports the pervasive nature of peroxisomal dysfunction affecting multiple organ systems, leading to a range of clinical manifestations.
PMID:33417210	SUPPORT	Peroxisomopathies are rare diseases due to dysfunctions of the peroxisome in which this organelle is either absent or with impaired activities. These diseases... affect the central and peripheral nervous system.	This statement aligns with the notion that peroxisomal dysfunction affects multiple organ systems.
PMID:26453805	SUPPORT	The peroxisomal compartment in hepatocytes hosts several essential metabolic conversions. These are defective in peroxisomal disorders... including mitochondria and the ER.	This reference details the involvement of multiple cellular compartments and metabolic pathways, illustrating multisystem impact.
PMID:1710072	SUPPORT	Several childhood multisystem disorders with prominent ophthalmological manifestations have been ascribed to the malfunction of the peroxisome, a subcellular organelle.	It categorizes peroxisomal disorders as multisystem with significant implications in different organ systems, particularly the eyes.
PMID:15868469	SUPPORT	Peroxisome biogenesis disorders, of which Zellweger syndrome is the most severe, result in severe neurological dysfunction associated with abnormal CNS neuronal migrations due to the lack of functional peroxisomes.	This echoes the impact on multiple organ systems but emphasizes the neurological dysfunctions.
PMID:21397417	SUPPORT	Peroxisomal disorders (PDs) are heterogeneous groups of diseases and affect many organs with varying degrees of involvement.	This source supports the statement by highlighting the multi-organ involvement in peroxisomal disorders.

0

category

Neurologic

name

Hypotonia

frequency

VERY_FREQUENT

evidence

reference	supports	snippet	explanation
PMID:7685145	SUPPORT	These disorders should be considered in the differential diagnosis of the infant with hypotonia and psychomotor delay...	The reference mentions hypotonia as a significant clinical feature in peroxisomal disorders.
PMID:28320181	PARTIAL	...suggest that these PEX10 mutations involve not only cerebellar but also more multiple nervous systems...	While the reference primarily discusses cerebellar involvement, it indirectly supports the statement by implicating neurological systems in PEX10-related peroxisome biogenesis disorders.
PMID:13129589	SUPPORT	The floppy infant syndrome is a well-recognized entity for pediatricians and neonatologists. The condition refers to an infant with generalized hypotonia...	The reference directly supports the very frequent occurrence of hypotonia in infants with peroxisomal disorders.
PMID:38409970	SUPPORT	Common clinical presentations include hypotonia, seizure, hepatomegaly, craniofacial dysmorphism and early death.	Hypotonia is listed as one of the common clinical presentations in Zellweger syndrome, a type of peroxisome biogenesis disorder.

1

category

Neurologic

name

Developmental Delay

frequency

VERY_FREQUENT

evidence

reference	supports	snippet	explanation
PMID:7685145	SUPPORT	Because peroxisomes are involved in the metabolism of lipids critical to the functioning of the nervous system, many of the peroxisomal disorders manifest with significant degrees of progressive psychomotor dysfunction.	The literature indicates that peroxisomal disorders, which include Peroxisome Biogenesis Disorders (PBDs), frequently present with progressive psychomotor dysfunction, supporting the statement that developmental delay is a very frequent neurologic phenotype.
PMID:36293220	SUPPORT	The clinical presentation of PBDs may range from severe, lethal multisystemic disorders to milder, late-onset disease. The vast majority of PBDs belong to Zellweger Spectrum Disordes (ZSDs) and represents a continuum of overlapping clinical symptoms.	Although this does not explicitly mention developmental delay, the overall description implies a frequent occurrence of neurologic dysfunction, which is often tied to developmental delays.
PMID:11769739	SUPPORT	Distinctive external features are variable among these three disorders, and neurologic deficit has its onset at birth or in infancy.	The article describes neurologic deficits appearing early in life, which aligns with developmental delays being a very frequent phenotype.
PMID:38409970	SUPPORT	Zellweger syndrome is an autosomal recessive disease within the spectrum of peroxisome biogenesis disorder manifesting in the neonatal period with profound dysfunction of the central nervous system, liver and kidney.	The mention of the neonatal onset of CNS dysfunction supports the frequent presence of developmental delays.
PMID:24172221	SUPPORT	Neurodevelopmental deficits and age-related occurrence of seizures are characteristic of RCDP and are related to the rest-activity in plasmalogen biosynthesis.	RCDP is a type of peroxisomal disorder, and its characteristic neurodevelopmental deficits support the statement about developmental delay being a common phenotype in PBDs.

2

category

Hepatobiliary

name

Hepatomegaly

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:31005404	PARTIAL	Inherited metabolic diseases account for about one third of pediatric patients with hepatomegaly, acute liver failure, cirrhosis or cholestasis.	The reference states that inherited metabolic diseases, which include peroxisome biogenesis disorders, account for a substantial portion of pediatric hepatomegaly cases but does not specify the frequency as 'frequent.'
PMID:22978395	PARTIAL	Liver pathology is a frequent finding in patients affected by a peroxisomal disorder.	The reference mentions liver pathology as frequent but does not specifically state hepatomegaly.
PMID:26615381	NO_EVIDENCE	ZS is a peroxisomal disorder with a multiple congenital anomalies, characterized by stereotypical facies, profound hypotonia, organ involvement including cerebral, retinal, hepatic, and renal.	The reference discusses organ involvement including hepatic involvement but does not specify hepatomegaly as frequent.

3

category

Visual

name

Retinopathy

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:31884631	SUPPORT	Retinopathy is a recurrent feature in both the severely and mildly affected patients, which can be accompanied with other ophthalmological pathologies.	The study states that retinopathy is a recurrent feature in patients with peroxisomal disorders, supporting the statement that visual phenotypes, specifically retinopathy, are frequent.
PMID:12473763	SUPPORT	Common to these three disorders are liver disease, variable neurodevelopmental delay, retinopathy, and perceptive deafness.	The study indicates that retinopathy is common in peroxisome biogenesis disorders like Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease, supporting the frequent occurrence of retinopathy as a visual phenotype.
PMID:35227579	SUPPORT	Retinal degeneration with or without optic atrophy is the most frequent phenotype, followed by oculomotor problems, involvement of the cornea and lens, and refractive errors.	The study states that retinal degeneration is the most frequent ocular phenotype observed in inherited metabolic disorders, which includes peroxisome biogenesis disorders, thereby supporting the frequent occurrence of retinopathy.
PMID:31254513	SUPPORT	Retinopathy leading to blindness is one of the major untreatable handicaps faced by patients with ZSD but is not well characterized.	The study highlights that retinopathy leading to blindness is a significant issue in patients with Zellweger Spectrum Disorder, a type of peroxisome biogenesis disorder, supporting the frequency of retinopathy as a visual phenotype.

4

category

Auditory

name

Hearing Loss

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:34534157	SUPPORT	The majority of PBD-ZSD patients in this study presented with moderately-severe to severe hearing loss.	This study characterizes hearing loss as a common phenotype in patients with Peroxisome Biogenesis Disorder within the Zellweger Spectrum.
PMID:36291074	SUPPORT	Peroxisome biogenesis disorders (due to PEX gene mutations) are associated with symptoms that range in severity and can lead to early childhood death, but a common feature is hearing impairment.	This study also confirms hearing impairment as a frequent phenotype in Peroxisome Biogenesis Disorders, further supporting the statement.
PMID:33417209	SUPPORT	Heimler syndrome is a rare syndrome associating sensorineural hearing loss with retinal dystrophy and amelogenesis imperfecta due to PEX1 or PEX6 biallelic pathogenic variations. This syndrome is one of the less severe forms of peroxisome biogenesis disorders.	Heimler syndrome, a less severe form of peroxisome biogenesis disorders, frequently presents with sensorineural hearing loss, further supporting the frequent association of hearing loss with these disorders.

5

category

Craniofacial

name

Craniofacial Dysmorphism

frequency

OCCASIONAL

evidence

reference	supports	snippet	explanation
PMID:23671347	SUPPORT	Patients with ZS present in the neonatal period with a characteristic phenotype of distinctive facial stigmata.	Distinctive facial stigmata can be considered a form of craniofacial dysmorphism, supporting the statement.
PMID:1710072	PARTIAL	Zellweger syndrome, the most lethal of the three peroxisomal biogenesis disorders, causes infantile hypotonia, seizures, and death within the first year.	While the text does not explicitly mention craniofacial dysmorphism, the severity of symptoms and multisystem involvement suggest potential craniofacial manifestations.

name	presence	evidence	context
Very Long Chain Fatty Acids (VLCFA)	Elevated	TRUNCATED	Diagnostic marker
Plasmalogens	Decreased	TRUNCATED	Diagnostic marker
Bile Acid Intermediates	Elevated	TRUNCATED	Diagnostic marker

0

name

PEX1

evidence

reference	supports	snippet	explanation
PMID:11545691	SUPPORT	The peroxisome is responsible for a variety of vital pathways in primary metabolism... Autism spectrum disorder of the Zellweger spectrum (ZSD) is a major subset of peroxisome biogenesis disorders (PBDs) that can be caused by mutations in any of the 14 PEX genes.	The statement is supported as it confirms that PBDs can be caused by mutations in any of the 14 PEX genes.
PMID:33955040	SUPPORT	Zellweger syndrome (ZS) is the foremost common and severe phenotype within the heterogeneous ZSD. However, missense mutations encode proteins with residual functions, which are associated with phenotypes that are milder than ZS. Mutations in the PEX1 gene are among the most prevalent.	The statement is supported as it mentions that mutations in the PEX1 gene are among the most prevalent causes of Zellweger syndrome, which is a type of PBD.

association

Pathogenic Variants

1

name

PEX6

evidence

reference	supports	snippet	explanation
PMID:17055079	SUPPORT	Defects in PEX genes impair peroxisome assembly and multiple metabolic pathways confined to this organelle, thus providing the biochemical and molecular bases of the peroxisome biogenesis disorders (PBD).	This statement indicates that mutations in PEX genes, including PEX6, are foundational to the development of peroxisome biogenesis disorders.
PMID:15858711	SUPPORT	Matsumoto and colleagues recently identified PEX26 as the gene responsible for complementation group 8 of the peroxisome biogenesis disorders... Here, we identify new PEX26 disease alleles, localize the PEX6-binding domain to the N-terminal half of the protein (aa 29-174), and show that, at the cellular level, PEX26 deficiency impairs peroxisomal import of both PTS1- and PTS2-targeted matrix proteins.	This paper discusses PEX26 in detail but also underscores the critical function of PEX6 in peroxisome biogenesis.
PMID:36980088	SUPPORT	Genetic testing revealed a mutation of the PEX6 (Peroxisomal Biogenesis Factor 6) gene, and the metabolic profile was consistent with the diagnosis.	This case report directly links pathogenic variants in PEX6 to a specific case of peroxisome biogenesis disorder.
PMID:33955040	SUPPORT	Autosomal recessive disorder of the Zellweger spectrum (ZSD) is a major subset of peroxisome biogenesis disorders (PBDs) that can be caused by mutations in any of the 14 PEX genes. Mutations in the PEX1 gene are among the most prevalent. PEX1 and PEX6 proteins, belonging to the AAA family of ATPases, form a hexameric complex, which is associated with peroxisome membranes and essential for peroxisome biology.	This paper confirms that mutations in PEX6, similar to those in PEX1, are linked to peroxisome biogenesis disorders.
PMID:10408779	SUPPORT	The PEX6 (peroxisome assembly factor-2, PAF-2) gene... restores peroxisome assembly in fibroblasts from peroxisome biogenesis disorder patients belonging to complementation group C (group 4 in the United States).	This research clarifies the structure and mutations of PEX6, noting its role in peroxisome biogenesis disorders.

association

Pathogenic Variants

2

name

Other PEX Genes

evidence

reference	supports	snippet	explanation
PMID:10904262	SUPPORT	Recent studies have identified the PEX genes that are mutated in 11 of the 12 known complementation groups of PBD patients.	This reference indicates that pathogenic variants in other PEX genes are associated with Peroxisome Biogenesis Disorder (PBD).
PMID:32399598	SUPPORT	For the first time, we show that pathogenic variants in PEX6 can present clinically as Perrault syndrome... PEX6 encodes a peroxisomal biogenesis factor.	Although this reference primarily discusses Perrault syndrome, it confirms that variants in PEX genes such as PEX6 are associated with peroxisomal biogenesis disorders.
PMID:34804114	SUPPORT	Pathogenic variants in the PEX26 gene lead to peroxisomal disorders of the full Zellweger spectrum continuum.	This reference highlights PEX26 gene variants contributing to peroxisomal disorders which fall under the broader category of peroxisome biogenesis disorders.
PMID:29070486	SUPPORT	The biogenesis of peroxisomes requires a category of proteins named peroxins, which are encoded by the PEX genes.	The reference supports that PEX genes are crucial for peroxisome biogenesis, implying that pathogenic variants can lead to related disorders.

association

Pathogenic Variants

0

name

Not Applicable

evidence

reference	supports	snippet	explanation
PMID:26305119	NO_EVIDENCE	In recent years, peroxisomes have emerged as important intracellular hubs for redox-, lipid-, inflammatory-, and nucleic acid-mediated signaling pathways. In this review, we focus on how nature and nurture modulate peroxisome biogenesis and function in mammalian cells.	The literature discusses the interplay of genetic, epigenetic, and environmental factors in peroxisome biogenesis and function but does not describe peroxisome biogenesis disorders as purely environmental.
PMID:30656921	NO_EVIDENCE	The disturbance of the peroxisome structure due to mutations in different PEX and non-PEX genes coding functional peroxisomal proteins is the pathogenic basis of the peroxisomal disorders.	The literature explains that peroxisome biogenesis disorders are due to genetic mutations, not environmental factors.

0

name

Symptomatic Management

description

Supportive care addressing specific symptoms such as physical therapy for hypotonia and seizure management.

evidence

reference	supports	snippet	explanation
PMID:11060787	PARTIAL	Treatment of PBD patients has generally involved only supportive care and symptomatic therapy.	The statement about supportive care and symptomatic therapy is accurate but does not explicitly mention physical therapy for hypotonia and seizure management.
PMID:38409970	PARTIAL	Despite an absence of treatment options, prompt diagnosis of Zellweger syndrome is important for providing appropriate symptomatic care.	The statement supports symptomatic care but does not detail specific treatments such as physical therapy for hypotonia or seizure management.

1

name

Nutritional Support

description

Specialized diet and supplements to manage biochemical abnormalities.

evidence

reference	supports	snippet	explanation
PMID:11060787	SUPPORT	A number of experimental therapies have been evaluated to determine whether or not correction of biochemical abnormalities through dietary supplementation and/or modification is of clinical benefit to PBD patients.	This snippet indicates that dietary supplementation and/or modification has been evaluated to manage biochemical abnormalities in PBD patients, supporting the statement that specialized diet and supplements can be a treatment strategy.
PMID:18758655	SUPPORT	The most important measures used to manage the intoxication present in many inborn errors of intermediate metabolism were presented (restriction of substrate build-up by means of diet or enzymatic inhibition, removal of toxic products, stimulation of residual enzyme activity, replacement of the deficient product).	This reference discusses the use of diet as a measure to manage biochemical abnormalities in metabolic disorders, including peroxisomal diseases, which supports the statement.
PMID:16819396	NO_EVIDENCE	Bile-acid therapy using oral cholic acid has proven effective in most of these bile acid synthetic defects making early diagnosis crucial to optimum clinical prognosis.	While this reference discusses a specific bile-acid therapy, it does not provide evidence about dietary or supplemental approaches for managing biochemical abnormalities in PBDs.

2

name

Liver Transplant

description

Considered in severe cases with significant liver dysfunction.

evidence

reference	supports	snippet	explanation
PMID:35331403	SUPPORT	Most of these disorders are currently treated by liver transplantation as standard of care.	The reference indicates that liver transplantation is the standard of care for congenital inherited hepatic disorders, which includes peroxisomal disorders like Peroxisome Biogenesis Disorder (PBD), supporting that liver transplant is considered in severe cases with significant liver dysfunction.
PMID:26615381	PARTIAL	ZS should be considered in the list of differential diagnosis in infants with stereotypical phenotype, neurodevelopmental delay, and severe hypotonia in association with liver and other organs involvement.	While this reference confirms liver involvement in Peroxisome Biogenesis Disorders such as Zellweger Syndrome, it does not specifically mention liver transplantation as a treatment.
PMID:22974902	PARTIAL	When none of the liver parenchyma is spared, or kidney insufficiency is marked, the only potentially curable treatment is liver transplantation (LT).	This reference supports the use of liver transplantation in severe liver conditions, though it does not directly mention Peroxisome Biogenesis Disorder.

3

name

Genetic Counseling

description

Providing information and support to families regarding inheritance and implications.

evidence

reference	supports	snippet	explanation
PMID:14619605	SUPPORT	Genetic counseling has developed as a discipline in response to the need to educate patients, families and professionals about genetic mechanisms and their application in health care. ... Genetic counseling is a process of medical education based upon empathy, patient autonomy and confidentiality in an atmosphere of empathy, support and understanding.	The literature describes genetic counseling as a discipline developed to educate patients, families, and professionals about genetic mechanisms and their application in healthcare, which supports the statement about providing information and support to families regarding inheritance and implications.
PMID:30237433	SUPPORT	Furthermore, it is also important to identify pre-symptomatic patients by family analysis of probands by providing appropriate disease information and genetic counseling, which will also lead to early intervention.	The literature discusses the importance of providing disease information and genetic counseling to families, supporting the statement about providing information and support to families regarding inheritance and implications in the context of peroxisomal diseases.

name	evidence
Autosomal recessive	TRUNCATED