Phenotype of adult Refsum disease due to a defect in peroxin 7

Horn, Morten Andreas; Brink, Daan M. van den; Wanders, Ronald J. A.; Durán, Marinus; Poll-Thé, Bwee Tien; Tallaksen, Chantal; Stokke, Oddvar; Moser, Hugo W.; Skjeldal, Ola H.

doi:10.1212/01.wnl.0000255960.01644.39

Cited by 35 publications

(24 citation statements)

References 10 publications

(8 reference statements)

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“…In the affected family members, impaired import of PHYH (and other PTS2 proteins) was indeed demonstrated, but apparently they display a milder phenotype than classical RCDP type 1 patients. In fact, one of the fi rst patients diagnosed by Refsum belongs to this group ( 85 ). Mutations in PEX7 are present, but these allow for some residual functional activity ( 83 ).…”

Section: Auxiliary Enzymes and Proteins Related To ␣ -Oxidationmentioning

confidence: 99%

Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism

Veldhoven

2010

Journal of Lipid Research

277

290

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Section: Auxiliary Enzymes and Proteins Related To ␣ -Oxidationmentioning

confidence: 99%

Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism

Veldhoven

2010

Journal of Lipid Research

277

290

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“…In ARD patients, plasma PA levels are usually >200 uM, and can be >1000 uM at diagnosis; PA can account for 5–30% of fatty acids in plasma and up to 50% in the liver [33]. Plasma and tissue PA levels in 3–5 month Pex7 neo/neo old mice were similar to that observed in ARD (Table 2).…”

Section: Resultsmentioning

confidence: 64%

A Pex7 hypomorphic mouse model for plasmalogen deficiency affecting the lens and skeleton

Braverman

Zhang

Chen

et al. 2010

Molecular Genetics and Metabolism

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Rhizomelic chondrodysplasia punctata type 1 is a peroxisome biogenesis disorder with the clinical features of rhizomelia, abnormal epiphyseal calcifications, congenital cataracts, and profound growth and developmental delays. It is a rare autosomal recessive disorder, caused by defects in the peroxisome receptor, Pex7. The pathology results from a deficiency of plasmalogens, a critical class of ether phospholipids whose functions are largely unknown. To study plasmalogens in an animal model, avoid early mortality and facilitate therapeutic investigations in this disease, we engineered a hypomorphic mouse model in which Pex7 transcript levels are reduced to less than 5% of wild type. These mice are born in expected ratios, are fertile and have a normal life span. However, they are petite and develop early cataracts. Further investigations showed delayed endochondral ossification and abnormalities in lens fibers. The biochemical features of reduced Pex7 function were reproduced in this model, including tissue plasmalogen deficiency, phytanic acid accumulation, reduced import of Pex7 ligands and consequent defects in plasmalogen biosynthesis and phytanic acid oxidation. Dietary supplementation with batyl alcohol, a plasmalogen precursor, recovered ether phospholipids in blood, but did not alter the clinical phenotype. The relatively mild phenotype of these mice mimics patients with milder pex7 defects, and highlights the skeleton and lens as sensitive markers of plasmalogen deficiency. The role of plasmalogens in the normal function of these tissues at various ages can now be studied and additional therapeutic interventions tested in this model.

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“…La majorité des patients présentent après l'âge de 30 ans un handicap moteur sévère dû à l'atteinte cérébelleuse et à la neuropathie périphérique, les fonctions cognitives sont normales. La rétinite pigmentaire conduit aussi souvent à une myopie sévère avec une vision tubulaire [25].…”

Section: Maladie De Refsum Adulteunclassified