The important role of biochemical and functional studies in the diagnostics of peroxisomal disorders

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

doi:10.1007/s10545-016-9922-4

Cited by 47 publications

(26 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 and VLCFAs and C26:0 lysophosphatidylcholine (C26:0 lysoPC) were measured in cultured cells as described previously 17 18. Peroxisomal β-oxidation of the VLCFA hexacosanoic acid (C26:0) and pristanic acid were measured as described 19.…”

Section: Methodsmentioning

confidence: 99%

ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…A deficiency of plasmalogen evoked by dysfunction of peroxisomal enzymes essential for the plasmalogen synthesis causes rhizomelic chondrodysplasia punctata (RCDP), a fatal genetic disease. To date, five distinct genotypes of RCDP have been identified . Inherited mutations in the genes encoding the enzymes essential for the synthesis of plasmalogens, including dihydroxyacetonephosphate acyltransferase (DHAPAT), alkylglycerone phosphate synthase (AGPS) and fatty acyl‐CoA reductase 1 (Far1), cause RCDP types 2 , 3 and 4 , respectively, whereas dysfunction of PEX7 and PEX5L , which are indispensable cytosolic factors for the transport of AGPS and other peroxisomal matrix proteins harboring peroxisome targeting signal type 2 , causes RCDP types 1 and 5 , respectively.…”

mentioning

confidence: 99%

Plasmalogen homeostasis – regulation of plasmalogen biosynthesis and its physiological consequence in mammals

Honsho

Fujiki

2017

FEBS Letters

View full text Add to dashboard Cite

Plasmalogens, mostly ethanolamine‐containing alkenyl ether phospholipids, are a major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of peroxisome biogenesis‐defective patients suggests that the de novo synthesis of plasmalogens plays a pivotal role in its homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the stability of fatty acyl‐CoA reductase 1 on peroxisomal membranes, a rate‐limiting enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of plasma membranes. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis by altering the stability of squalene monooxygenase, a key enzyme in cholesterol biosynthesis, implying physiological consequences of plasmalogen homeostasis with respect to cholesterol metabolism in cells, as well as in organs such as the liver.

show abstract

“…95,96 Assays have been described that measure peroxisomal enzyme activities in patient fibroblasts, usually using radioisotope-labeled substrates. 127 Only phytanic acid oxidase and pristanic acid oxidase are routinely offered clinically. Fibroblasts can be used to assess the cellular distribution of the enzyme catalase (catalase solubility), which is normally localized to peroxisomes; catalase localization to the cytosol is a sensitive marker of peroxisomal dysfunction.…”

Section: Analysis Of Pipecolic Acid In Urine and Plasmamentioning

confidence: 99%

Laboratory diagnosis of disorders of peroxisomal biogenesis and function: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Biase

Tortorelli

Kratz

et al. 2020

Genetics in Medicine

View full text Add to dashboard Cite

Disclaimer: This technical standard is designed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to this standard is voluntary and does not necessarily assure a successful medical outcome. This standard should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with this standard. They also are advised to take notice of the date any particular standard was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures. 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 clinical presentations. The inclusion of X-linked adrenoleukodystrophy to the Recommended Uniform Screening Panel for newborn screening programs in the United States may increase detection of this and other peroxisomal disorders. The current diagnostic approach relies heavily on biochemical genetic tests measuring peroxisomal metabolites, including very long-chain and branched-chain fatty acids in plasma and plasmalogens in red blood cells. Molecular testing can confirm biochemical findings and identify the specific genetic defect, usually utilizing a multiple-gene panel or exome/genome approach. When next-generation sequencing is used as a first-tier test, evaluation of peroxisome metabolism is often necessary to assess the significance of unknown variants and establish the extent of peroxisome dysfunction. This document provides a resource for laboratories developing and implementing clinical biochemical genetic testing for peroxisomal disorders, emphasizing technical considerations for sample collection, test performance, and result interpretation. Additionally, considerations on confirmatory molecular testing are discussed.

show abstract

The important role of biochemical and functional studies in the diagnostics of peroxisomal disorders

Cited by 47 publications

References 61 publications

ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism

ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism

Plasmalogen homeostasis – regulation of plasmalogen biosynthesis and its physiological consequence in mammals

Laboratory diagnosis of disorders of peroxisomal biogenesis and function: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Contact Info

Product

Resources

About