Abstract
In recent years a number of biochemical abnormalities have been described in patients with the infantile form of Refsum disease, including the accumulation of very long chain fatty acids, trihydroxycoprostanoic acid and pipecolic acid. In this paper we show that catalase-containing particles (peroxisomes), alkyl dihydroxyacetone phosphate synthase and acyl-CoA oxidase protein are deficient in patients with infantile Refsum disease. These findings suggest that in the infantile form of Refsum disease, as in the cerebro-hepato-renal (Zellweger) syndrome the multiplicity of biochemical abnormalities is due to a deficiency of peroxisomes and hence to a generalized loss of peroxisomal functions. As a consequence the infantile form of Refsum disease can be diagnozed biochemically by methods already available for the prenatal and postnatal diagnosis of the cerebro-hepato-renal (Zellweger) syndrome.
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Boltshauser E, Spycher MA, Steinmann B, Briner J, Isler W, Kuster T, Poulos A, Pollard AC (1982) Infantile phytanic acid storage disease: a variant of Refsum disease? Eur J Pediatr 139:317–318
Borst P (1983) Animal peroxisomes (microbodies), lipid biosynthesis and the Zellweger syndrome. Trends Biochem Sci 8:269–272
Brown AJ, Snyder F (1983) The mechanism of alkyldihydroxyacetone phosphate synthase. J Biol Chem 258:4184–4189
Datta NS, Wilson GN, Hajra AK (1984) Deficiency of enzymes catalyzing the biosynthesis of glycerol-ether lipids in Zellweger syndrome. N Engl J Med 311:1080–1083
Goldfischer S, Moore CL, Johnson AB, Spiro AJ, Valsamis LM, Wisniewski HK, Ritch RH, Norton WT, Rapin I, Gratner LM (1973) Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. Science 182:62–64
Goldfischer S, Reddy JK (1984) Peroxisomes (microbodies) in cell pathology. Int Rev Exp Pathol 26:45–84
Hajra AK, Burke CL, Jones CL (1979) Subcellular localization of acyl-coenzyme A: dihydroxyacetone phosphate acyltransferase in rat liver peroxisomes (microbodies). J Biol Chem 254:10896–10900
Jones CL, Hajra AK (1980) Properties of guinea pig liver peroxisomal dihydroxyacetone phosphate acyltransferase. J Biol Chem 255:8289–8295
Kase F, Björkhem I, Pedersen JI (1983) Formation of cholic acid from trihydroxycoprostanoic acid by rat liver peroxisomes. J Lipid Res 24:1560–1567
Kelley RI (1983) The cerebro-hepato-renal syndrome of Zellweger syndrome, morphological and metabolic aspects. Am J Med Genet 16:503–517
Mortensen PB, Kolvraa S, Gregersen N, Rasmussen K (1982) Cyanide-insensitive and clofibrate enhanced β-oxidation of diodecanedioic acid in rat liver. An indication of peroxisomal β-oxidation of dicarboxylic acids. Biochim Biophys Acta 713:393–397
Poulos A, Sharp P (1984) Plasma and skin fibroblasts C26 fatty acids in infantile Refsum's disease. Neurology 34:1606–1609
Poulos A, Whiting MJ (1985) Indentification of 3 α, 7 α, 12 α-trihydroxy-5 β-cholestan-26-oic acid, an intermediate in cholic acid synthesis, in the plasma of patients with infantile Refsum's disease. J Inher Metab Dis 8:13–17
Poulos A, Sharp P, Whiting MJ (1984) Infantile Refsum's disease (phytanic acid storage disease). A variant of Zellweger syndrome? Clin Genet 26:579–586
Poulos A, Pollard AC, Mitchell JD, Wise D, Mortimer G (1984) Patterns of Refsum's disease. Phytanic acid oxidase deficiency. Arch Dis Child 59:222–229
Refsum S (1946) Heredopathia atactica polyneuritiformis. A familial syndrome not hitherto described. Contribution to the hereditary diseases of the nervous system. Acta Psychiatr Neurol [Suppl] 38:1–303
Schrakamp G, Roosenboom CFP, Schutgens RBH, Wanders RJA, Heymans HSA, Tager JM, van den Bosch H (1985) Alkyl dihydroxyacetone phosphate synthase in human fibroblasts and its deficiency in Zellweger syndrome. J Lipid Res 26:867–873
Schutgens RBH, Romeyn GJ, Wanders RJA, van den Bosch H, Schrakamp G, Heymans HSA (1984) Deficiency of acyl-CoA: dihydroxyacetone phosphate acyltransferase in patients with Zellweger (cerebro-hepato-renal) syndrome. Biochem Biophys Res Commun 120:179–184
Scotto JM, Hadchouel M, Odièvre M, Laudat MH, Saudubray JM, Dulac O, Beucler I, Beaune P (1982) Infantile phytanic acid storage disease, a possible variant of Refsum's disease: three cases, including ultrastructural studies of the liver. J Inher Metab Dis 5:83–90
Singh I, Moser AE, Goldfischer S, Moser HW (1984) Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy. Proc Natl Acad Sci USA 81:4203–4207
Steinberg D (1983) Phytanic acid storage disease: Refsum's syndrome. In: Stanbury JB, Wijngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds), The metabolic basis of inherited disease, McGraw-Hill, New York, pp 731–747
Stokke O, Skrede S, Ek J, Björkhem I (1984) Refsum's disease, adrenoleucodystrophy, and the Zellweger syndrome. Scand J Clin Lab Invest 44:463–464
Tager JM, Ten Harmsen van der Beek WA, Wanders RJA, Hashimoto T, Heymans HSA, van den Bosch H, Schutgens RBH, Schram AW (1984) Peroxisomal β-oxidation enzyme proteins in the Zellweger syndrome. Biochem Biophys Res Commun 126:1269–1275
Wanders RJA, Kos M, Roest B, Meijer AJ, Schrakamp G, Heymans HSA, Tegelaers WHH, van den Bosch H, Schutgens RBH, Tager JM (1984) Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome. Biochem Biophys Res Commun 123:1054–1061
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Wanders, R.J.A., Schutgens, R.B.H., Schrakamp, G. et al. Infantile Refsum disease: deficiency of catalase-containing particles (peroxisomes), alkyldihydroxyacetone phosphate synthase and peroxisomal β-oxidation enzyme proteins. Eur J Pediatr 145, 172–175 (1986). https://doi.org/10.1007/BF00446057
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DOI: https://doi.org/10.1007/BF00446057