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... 

Sterol-A -isomerase deficiency, known as Conradi-HUnermann syndrome (CDPX2), is an X-linked dominant disorder. Clinical manifestations of this disorder include skeletal abnormalities, chondrodysplasia punctata, craniofacial anomalies, cataracts, and skin abnormalities. The 7-dehydrocholesterol reductase deficiency, known as Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder occurring in about 1 in 20,000 births. Clinical manifestations of affected individuals include craniofacial abnormalities, microcephaly, congenital heart disease, malformation of the limbs, psychomotor retardation, cerebral maldevelopment, and urogenital anomalies. Measurement of 7-dehydrocholesterol in amniotic fluid during second trimester or in neonatal blood specimen has been useful in the identification of the disorder. The sterol-A " -reductase deficiency causes a developmental phenotype similar to SLO syndrome and is associated with accumulation of desmosterol. The inability of de novo fetal synthesis of cholesterol combined with its inadequate transport from the mother to the fetus appears... 

J. M. J. Derry, E. Gormally, G. D. Means, et al. Mutations in a A -A sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. Nature Genetics 22, 286 (1999). 

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. 

Spranger JW, Opitz JM, Bidder U. Heterogeneity of Chondrodysplasia punctata. Humangenetik 1971 11(3) 190-212. 

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. 

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

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. 

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