Laboratory Diagnosis of Peroxisomal Disorders in the -Omics Era and the Continued Importance of Biomarkers and Biochemical Studies

Wanders, Ronald J. A.; Vaz, Frédéric M.; Ferdinandusse, Sacha; Kemp, Stephan; Ebberink, Merel S.; Waterham, Hans R.

doi:10.1177/2326409818810285

Cited by 5 publications

(4 citation statements)

References 73 publications

(111 reference statements)

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“…Os peroxissomos são organelas necessárias para diversas funções metabólicas como degradação de ácidos graxos de cadeia muito longa, síntese de ácidos biliares, produção de plasmalógenos, entre outros 7 .…”

Section: Discussionunclassified

Uso de canabidiol como terapia adjuvante em paciente com síndrome de Zellweger: relato de caso

Oliveira¹,

Machado²,

Fóla³

et al. 2020

Medicina (Ribeirão Preto)

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Também denominada síndrome cerebrohepatorenal, a síndrome de Zellweger é uma doença autossômica recessiva rara, pertencente ao espectro de erros inatos do metabolismo que afetam os peroxissomos. São causados principalmente por mutações em qualquer um dos 14 genes PEX diferentes que codificam para proteínas envolvidas na montagem do peroxissoma, sendo a mais comum do PEX1. O quadro clínico geralmente é observado no período neonatal e primeira infância, incluindo alterações faciais, hipotonia profunda e ausência de reflexos neonatais, além de disfagia, disfunção hepática e convulsões. O diagnóstico é feito a partir da clínica e testes bioquímicos e confirmados pela visualização da mutação em um dos 14 genes PEX. Como não há tratamento específico, é feito tratamento sintomático. Nosso paciente masculino de 1 ano e 9 meses apresentou a hipotonia congênita como sintoma marcante, além de crises convulsivas recorrentes logo após o nascimento. Evoluiu com necessidade de gastrostomia e estagnação de marcos neuromotores. O diagnóstico foi confirmado aos seis meses, através da dosagem de ácidos graxos de cadeia longa. Crises convulsivas evoluíram de maneira refratária a diversos anticonvulsivantes e com elevada frequência diária, por isso iniciamos canabidiol (CBD-RSHO GOLD) por via enteral que reduziu significantemente as crises. Não há tratamento definitivo para esta enfermidade, sendo importante tratamento sintomático das crises convulsivas e terapias de reabilitação, nesse caso, o uso de (CBD- RSHO GOLD) provocou uma redução de 92% na frequência de crises diárias do paciente. No entanto, não é possível concluir, ainda, melhoras em outros sinais e sintomas.

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Section: Discussionunclassified

Uso de canabidiol como terapia adjuvante em paciente com síndrome de Zellweger: relato de caso

Oliveira¹,

Machado²,

Fóla³

et al. 2020

Medicina (Ribeirão Preto)

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“…Peroxisomes are single-membrane subcellular organelles, found in all eukaryotic cells, participating in the range of metabolic pathways such as α- and β-oxidation of very long fatty acids, the synthesis of bile acids, detoxification of glyoxylate and H 2 O 2 metabolism [ 61 , 62 ]. Peroxisomal enzymes, such as xanthine oxidase and acyl-CoA oxidases, are involved in ROS generation [ 63 ].…”

Section: Metabolic Pathways As Sources Of Ros Generation In Cellsmentioning

confidence: 99%

The Effect of β-Carotene, Tocopherols and Ascorbic Acid as Anti-Oxidant Molecules on Human and Animal In Vitro/In Vivo Studies: A Review of Research Design and Analytical Techniques Used

et al. 2022

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Prolonged elevated oxidative stress (OS) possesses negative effect on cell structure and functioning, and is associated with the development of numerous disorders. Naturally occurred anti-oxidant compounds reduce the oxidative stress in living organisms. In this review, antioxidant properties of β-carotene, tocopherols and ascorbic acid are presented based on in vitro, in vivo and populational studies. Firstly, environmental factors contributing to the OS occurrence and intracellular sources of Reactive Oxygen Species (ROS) generation, as well as ROS-mediated cellular structure degradation, are introduced. Secondly, enzymatic and non-enzymatic mechanism of anti-oxidant defence against OS development, is presented. Furthermore, ROS-preventing mechanisms and effectiveness of β-carotene, tocopherols and ascorbic acid as anti-oxidants are summarized, based on studies where different ROS-generating (oxidizing) agents are used. Oxidative stress biomarkers, as indicators on OS level and prevention by anti-oxidant supplementation, are presented with a focus on the methods (spectrophotometric, fluorometric, chromatographic, immuno-enzymatic) of their detection. Finally, the application of Raman spectroscopy and imaging as a tool for monitoring the effect of anti-oxidant (β-carotene, ascorbic acid) on cell structure and metabolism, is proposed. Literature data gathered suggest that β-carotene, tocopherols and ascorbic acid possess potential to mitigate oxidative stress in various biological systems. Moreover, Raman spectroscopy and imaging can be a valuable technique to study the effect of oxidative stress and anti-oxidant molecules in cell studies.

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“…For an overview, also about those PEX10 cases with a severe phenotype, we refer to standard textbooks and informative reviews. [1][2][3] Case Report A 4-year-old boy from a nonconsanguineous Albanian family without remarkable history presented with a subacute cerebellar ataxia. His personal history was uneventful except for a premature closure of the sagittal suture, not requiring an intervention.…”

Section: Introductionmentioning

confidence: 99%

“…For an overview, also about those PEX10 cases with a severe phenotype, we refer to standard textbooks and informative reviews. 1 2 3…”

Section: Introductionmentioning

confidence: 99%

How to Detect Isolated PEX10-Related Cerebellar Ataxia?

et al. 2022

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A 4-year-old boy presented with subacute onset of cerebellar ataxia. Neuroimaging revealed cerebellar atrophy. Metabolic screening tests aiming to detect potentially treatable ataxias showed an increased value (fourfold upper limit of normal) for phytanic acid and elevated very-long-chain fatty acid (VLCFA) ratios (C24:0/C22:0 and C26:0/C22:0), while absolute concentrations of VLCFA were normal. Genetic analysis identified biallelic variants in PEX10. Immunohistochemistry confirmed pathogenicity in the patients' cultured fibroblasts demonstrating peroxisomal mosaicism with a general catalase import deficiency as well as conspicuous peroxisome morphology as an expression of impaired peroxisomal function. We describe for the first time an elongated peroxisome morphology in a patient with PEX10-related cerebellar ataxia.A literature search yielded 14 similar patients from nine families with PEX10-related cerebellar ataxia, most of them presenting their first symptoms between 3 and 8 years of age. In 11/14 patients, the first and main symptom was cerebellar ataxia; in three patients, it was sensorineural hearing impairment. Finally, all 14 patients developed ataxia. Polyneuropathy (9/14) and cognitive impairment (9/14) were common associated findings. In 12/13 patients brain MRI showed cerebellar atrophy. Phytanic acid was elevated in 8/12 patients, while absolute concentrations of VLCFA levels were in normal limits in several patients. VLCFA ratios (C24:0/C22:0 and/or C26:0/C22:0), though, were elevated in 11/11 cases. We suggest including measurement of phytanic acid and VLCFA ratios in metabolic screening tests in unexplained autosomal recessive ataxias with cerebellar atrophy, especially when there is an early onset and symptoms are mild.

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Laboratory Diagnosis of Peroxisomal Disorders in the -Omics Era and the Continued Importance of Biomarkers and Biochemical Studies

Cited by 5 publications

References 73 publications

Uso de canabidiol como terapia adjuvante em paciente com síndrome de Zellweger: relato de caso

Uso de canabidiol como terapia adjuvante em paciente com síndrome de Zellweger: relato de caso

The Effect of β-Carotene, Tocopherols and Ascorbic Acid as Anti-Oxidant Molecules on Human and Animal In Vitro/In Vivo Studies: A Review of Research Design and Analytical Techniques Used

How to Detect Isolated PEX10-Related Cerebellar Ataxia?

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