Acyl-CoA oxidases deficiency

Acyl-CoA oxidase deficiency D-bifunctional protein deficiency Racemase deficiency Refsum s disease... 

Unfortunately, a minority of the patients with peroxisomal dysfunction cannot be diagnosed using plasma parameters. In the authors laboratory, patients have been seen with peroxisome biogenesis defects, D-bifunctional protein deficiency, and acyl-CoA oxidase deficiency in whom no abnormalities of plasma VLCFA, phytanic acid, pristanic acid or bile acids could be established. Hence, a strong clinical suspicion of peroxisomal disease should always be verified by fibroblast investigation, regardless of the outcome of plasma analyses. 

Meyer, K., Lee, J. S., Dyck, P. A., Cao, W. Q., Rao, M. S., Thorgeirsson, S. S., and Reddy, J. K. (2003). Molecular profiling of hepatocellular carcinomas developing spontaneously in acyl-CoA oxidase deficient mice comparison with Uver tumors induced in wild-type mice by a peroxisome proliferator and a genotoxic carcinogen. Carcinogenesis 24, 975-984. 

Straight-chain acyl-CoA oxidase deficiency (AOxI) D-bifunctional protein (DBP)... 

Four defined disorders of peroxisomal jff-oxidation have been identified including (1) X-linked adrenoleukodystrophy/adrenomyeloneuropathy, (2) acyl-CoA oxidase deficiency (3) D-bifunctional protein deficiency and (4) peroxisomal thiolase deficiency. The clinical presentation of the latter 3 disorders resembles that of the disorders of peroxisome biogenesis whereas the clinical presentation of X-linked ALD/AMN patients is completely different which explains why it is better to discuss this entity separately under d. 

Acyl-CoA oxidase deficiency was first described in 1988 by Poll-The et al. [4] under the name pseudo-neonatal adrenoleukodystrophy since the 2 patients described had the typical signs and symptoms described for neonatal adrenoleukodystrophy by Kelley et al. [5]. However, peroxisomes were present in the patients liver albeit of enlarged size. In addition THCA and DHCA were completely normal. 

Peroxisomal fatty acid y9-oxidation deficiencies Acyl-CoA oxidase deficiency and D-bifunctional protein deficiency have both been resolved at the molecular level [10] and many often private mutations have been identified. The same is true for Refsum disease and 2-methylacyl-CoA racemase deficiency [16]. 

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. 

Group 2 contains the single peroxisomal enzyme deficiencies [14]. This group is also subdivided in different classes, including the peroxisomal beta-oxidation deficiencies (X-linked adrenoleucodystrophy, X-ALD), acyl-CoA oxidase 1 deficiency... 

Qi, C., Zhu, Y., Pan, J., Usuda, N., Maeda, N., Yeldandi, A. V., Rao, M. S., Hashimoto, T., and Reddy, J. K. Absence of spontaneous peroxisome proliferation in enoyl-CoA Hydratase/L-3-hydroxyacyl-CoA dehydrogenase-deficient mouse liver. Further support for the role of fatty acyl CoA oxidase in PPARalpha ligand metabolism. J Biol Chem 274 (1999) 15775-15780. 

Pristanic acid is a 2-methyl fatty acid which undergoes exclusive oxidation in the peroxisome. Indeed, pristanic acid oxidation is strongly deficient in Zellweger cells lacking peroxisomes. On the other hand, normal oxidation rates were found in patients with an inherited deficiency of acyl-CoA oxidase, suggesting the existence of a different acyl-CoA oxidase (see later). 

Following the initial report by PoU-The et al. of two patients with a clinical presentation strongly resembling neonatal adrenoleukodystrophy, very few additional patients have been descrihed. In these patients the straight-chain acyl-CoA oxidase is deficient resulting in the deficient oxidation of C26 0 only, with normal oxidation of branched-chain fatty acids which explains the normal levels of pristanic acid and the bile acid intermediates in these patients. 

Acyl-Co A oxidase deficiency (pseudo-neonatal adrenoleukodystrophy) Straight-chain acyl-CoA oxidase (SCOX) Generalized 17q25 264470... 

In line with this notion, pristanic acid, DHCA and THCA are completely normal in patients with straight-chain acyl-CoA oxidase (SCOX/ACOXl = enzyme 1 in Fig. 25.2) deficiency. 

Poll-The BT, Roels F, Ogier H, Scotto J, Vamecq J, Schiitgens RBH et al. A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). Am J Hum Genet 1988 42(3) 422-434. 

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