Rhizomelic chondrodysplasia punctata

ALDP, DHAP, dihydroxyacetone phosphate DHAPAT, dihydroxyacetone phosphate acyltransferase NALD, neonatal adrenoleukodystrophy RCDP, rhizomelic chondrodysplasia punctata X-ALD, X-linked adrenoleukodystrophy ZS, Zellweger s syndrome. 

Alkyl PAT, alkyl-dihydroxy phosphate synthase Bif, bifunctional enzyme DHAPAT, dihydroxyphosphate acyltransferase deficiency DHCA, dihydroxycholestanoic acid N, normal nd, not determined Ox, acyl-CoA oxidase Rac, 2-methylacyl-CoA racemase RCDP, rhizomelic chondrodysplasia punctata Ref, Refsum s disease THCA, trihydroxycholestanoic acid VLCFA, very-long-chain fatty acid. 

Braverman, N., Chen, L., Lin, P. et al. Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. Hum. Mutat. 20 284-297, 2002. 

PDHC pyruvate dehydrogenase complex RCDP rhizomelic chondrodysplasia punctata... 

Classical rhizomelic chondrodysplasia punctata (RCDP) patients have a marked shortening of their proximal extremities, calcified stippling of the epiphyses and cataracts in addition to their absent psychomotor development. Patients with a variant form of RCDP have normal bones, but will have cataracts and some degree of mental retardation. Patients with a deficiency of dihydroxyacetone phosphate acyltransferase are clinically indistinguishable from the classical RCDP phenotype. 

Table 3.4.1 Levels of very-long-chain fatty acids (VLCFA), pristanic acid and phytanic acid in the different peroxisomal disorders. AMACR 2-methyl acyl-CoA racemase, N normal, RCDP rhizomelic chondrodysplasia punctata, SCP-x sterol carrier protein, ZSDs Zellweger spectrum disorders,...

Cerebrohepatorenal (Zellweger s) syndrome Infantile Refsum s disease Neonatal adrenoleukodystrophy Rhizomelic chondrodysplasia punctata Hyperpipecolic acidemia Genetic diseases with generalized impairment of peroxisomal function but normal number of peroxisomes... 

Braverman N, Steel G, Obie C, Moser A, Moser H, Gould SJ, et al. Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nature Genet 1997 15(4) 369-376. 

Rhizomelic chondrodysplasia punctata (CDP) Pex7 peroxisomal enzyme import... 

Rhizomelic chondrodysplasia punctata Type 1 (RCDP) Peroxisomal biogenesis disorder... 

Pahan, K., Khan, M. Singh, I. (19%) J. LipidRes. 37, 1137-1143. Phytanic acid oxidation normal activation and transport yet defective a-hydroxylation of phytanic acid in peroxisomes Irom Refsum disease and rhizomelic chondrodysplasia punctata. 

Rhizomelic Chondrodysplasia Punctata Type 1 (RCDP Type I). Patients suffering from RCDP type I which is due to a non-fiinetional PTS2-receptor, also show deficient oxidations of phytanic acid. Recent data show that this results from a deficiency of phytanoyl-CoA hydroxylase. The deficiency of PhyH probably results from its mis-locahzation to the cytosol as a consequence of the non-functional PTS2-receptor and the apparent instability of the PhyH-protein in the cydosol. Pulse/chase experiments are underway to resolve this. 

Purdue, P.E., Zhang, J.W., Skoneczny, M. Lazarow, PJ3. (1997) Nat Genet 15, 381-384. Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor. 

Jansen, G.A., Mihalik, S.J, Watkins, P.A., Moser, H.W., Jakobs, C, Heijmans, H.S. Wanders, R.J. (1997)7. Inherit. Metab. Dis. 20,444-446. Phytanoyl-CoA hydroxylase is not only deficient in classical Refsum disease but also in rhizomelic chondrodysplasia punctata. 

Phytanic acid levels in neonates are not reliable, because its dietary intake has been insufficient by definition. In older patients it is important to evaluate the levels of both branched-chain fatty acids an increase of phytanic acid with a decrease of pristanic acid suggests either Refsum disease or rhizomelic chondrodysplasia punctata. All other peroxisomal defects will show an increase of both analytes. 

Rhizomelic) chondrodysplasia punctata (RCDP) type 1 Pex7p Generalized 6q22-q24 215100... 

Table 25,2, Rhizomelic chondrodysplasia punctata type 1 CPex7-deficiency) (25,5), type 2 (DHAPAT deficiency) (25,6) and type 3 (alkyl-DHAP synthase deficiency) (25.7) classical forms (80/10/10 patients) ...

Rhizomelic chondrodysplasia punctata the three genes underlying RCDP types 1, 2 and 3 have been identified and molecular analysis is now possible for all 3 forms (see [10]). 

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