Disease relevance of Chondrodysplasia Punctata, Rhizomelic

• Genetic relation between the Zellweger syndrome, infantile Refsum's disease, and rhizomelic chondrodysplasia punctata [1].
• In contrast, normal DHA synthesis was observed in cells from patients with rhizomelic chondrodysplasia punctata, Refsum disease, X-linked adrenoleukodystrophy, and deficiency of mitochondrial medium- or very long-chain acyl-CoA dehydrogenase [2].
• Recently, however, phytanic acid has also been found in peroxisomal disorders (Zellweger's syndrome, neonatal adrenoleukodystrophy, infantile Refsum's syndrome, rhizomelic chondrodysplasia punctata) [3].
• The second group includes diseases with a unique manifestation, such as X-linked adrenoleukodystrophy, hyperoxaluria type I and rhizomelic chondrodysplasia punctata [4].
• She had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia [5].

High impact information on Chondrodysplasia Punctata, Rhizomelic

• Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata [6].
• Reduced survival was observed in cells deficient in plasmalogens (rhizomelic chondrodysplasia punctata) and in cells deficient in peroxisomal fatty acid oxidation (bifunctional enzyme deficiency), which accumulated pyrene-fatty acids [7].
• Pex7p function is conserved between yeasts and humans, with defects in the human protein causing rhizomelic chondrodysplasia punctata (RCDP), a severe, lethal peroxisome biogenesis disorder characterized by aberrant targeting of several PTS2 peroxisomal proteins, but uncertainty remains about the subcellular localization of this receptor [8].
• In addition, we used PpPex7p as a model protein to understand the effect of the Pex7p mutations found in human patients with rhizomelic chondrodysplasia punctata [9].
• Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata [10].

Chemical compound and disease context of Chondrodysplasia Punctata, Rhizomelic

• In the blood spot from a patient with rhizomelic chondrodysplasia punctata, the concentration of phytanic acid was increased, whereas pristanic acid was within the control range, resulting in a low pristanic acid/phytanic acid ratio [11].
• In plasma from healthy individuals and from patients with Refsum's disease, 2-hydroxyphytanic acid was found at levels less than 0.2 mumol/l, whereas the acid accumulated in plasma from patients with rhizomelic chondrodysplasia punctata, generalized peroxisomal dysfunction, and a single peroxisomal beta-oxidation enzyme deficiency [12].
• Our data indicate that the genetic defect in rhizomelic chondrodysplasia punctata results in abnormalities in two apparently unrelated pathways (i.e., phytanic acid oxidation and ether lipid biosynthesis [13].
• Rhizomelic chondrodysplasia punctata, its recently identified variant form and glutaryl-CoA oxidase deficiency will show no abnormalities and must be identified by other means [14].
• Studies of vertebral coronal cleft in rhizomelic chondrodysplasia punctata [15].

Biological context of Chondrodysplasia Punctata, Rhizomelic

• We investigated the molecular dysfunction of Pex7p variants in mammals, including Pex7p-W221ter and Pex7p with one site mutation at G217R, A218V, or L292ter, which frequently occurs in the human fatal genetic peroxisomal disease rhizomelic chondrodysplasia punctata, showing a cell phenotype of PTS2 import defect [16].
• Peroxisomes were studied in the liver of two rhizomelic chondrodysplasia punctata patients using electron microscopy and catalase cytochemistry [17].
• In cells from patients with a defective alpha-oxidation (Refsum disease, rhizomelic chondrodysplasia punctata and generalized peroxisomal disorders) 2-hydroxyphytanic acid and pristanic acid were low or not detectable, showing that in these disorders the hydroxylation of phytanoyl-CoA to 2-hydroxyphytanoyl-CoA is deficient [18].
• Clinically, peroxisome biogenesis disorders (PBDs) are a group of lethal diseases with a continuum of severity of clinical symptoms ranging from the most severe form, Zellweger syndrome, to the milder forms, infantile Refsum disease and rhizomelic chondrodysplasia punctata [19].

Anatomical context of Chondrodysplasia Punctata, Rhizomelic

• The GFP fusion proteins, tagged at either the N- or C-terminus, were able to restore PTS2 import in rhizomelic chondrodysplasia punctata fibroblasts, and Pex7p-GFP was located both in the lumen of peroxisomes and in the cytosol [20].
• Cerebellar atrophy in chronic rhizomelic chondrodysplasia punctata: a potential role for phytanic acid and calcium in the death of its Purkinje cells [21].
• In fibroblasts from a child with rhizomelic chondrodysplasia punctata the rate of degradation of U-3H- and 1-14C-labelled phytanic acid was markedly reduced whereas the rate of degradation of U-3H-labelled pristanic acid was normal [22].
• A boy with rhizomelic chondrodysplasia punctata, diagnosed on the laboratory evidence of a high plasma concentration of phytanic acid and a low erythrocyte concentration of plasmalogens, has been followed from birth to the age of 16 years [23].

Gene context of Chondrodysplasia Punctata, Rhizomelic

• Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor [24].
• PEX7 mutations cause the peroxisome biogenesis disorder (PBD) rhizomelic chondrodysplasia punctata (RCDP) [25].
• In Zellweger syndrome and rhizomelic chondrodysplasia punctata fibroblast cell lines, in which alkyl-DHAP synthase cannot be imported into peroxisomes, the enzyme was mainly detected in its precursor form [26].
• Greater reduction in DHAP-synthase activity, but only a partial reduction in DHAP-AT activity was observed in rhizomelic chondrodysplasia punctata [27].
• Patients with the autosomal recessive form of rhizomelic chondrodysplasia punctata (AR-RCDP) and other generalized peroxisomal disorders are deficient in the incorporation of fatty alcohol into plasmalogen lipids [28].

References