Abstract
We describe a 16-year-old boy suffering from psychomotor retardation, sensorineuronal hearing impairment, peripheral neuropathy, hepatosplenomegaly, short stature and delayed puberty. Postnatally, muscular hypotonia, mild facial dysmorphism and delayed fontanelle closure had been noticed. At the time of our examination, adrenal cortical function was normal. Biochemical analysis revealed accumulation of very long (>C22) chain fatty acids in plasma and fibroblasts. Furthermore, elevated levels of intermediates of bile acid synthesis and phytanic acid were detectable. These findings are consistent with a defect in the peroxisomal β-oxidation system. A generalised defect of peroxisomal function was excluded by normal plasmalogen levels in erythrocytes and normal plasmalogen de novo synthesis in fibroblasts. Immunoblotting of the peroxisomal β-oxidation enzymes gave normal results suggesting retained immunoreactivity but catalytic inactivity of one of the enzymes involved, probably either the trifunctional protein or the peroxisomal ketothiolase. This case markedly differs clinically from the few published reports on isolated deficiencies of peroxisomal β-oxidation. Among the patients with comparable biochemical findings, this is the first report of survival into adolescence.
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Abbreviations
- N-ALD:
-
neonatal adrenoleukodystrophy
- VLCFA:
-
very long chain fatty acids
- X-ALD:
-
X-chromosomal adrenoleukodystrophy
- ZS:
-
Zellweger syndrome
References
Barth PG, Schutgens RBH, Bakkeren JAJM, Dingemans KP, Heymans HSA, Douwes AC, Klei-an Moorsel JM van der (1985) A milder variant of Zellweger syndrome. Eur J Pediatr 144: 338–342
Barth PG, Wanders RJA, Schutgens RBH, Bleeker-Wagemakers EM, Heemstra D van (1990) Peroxisomal β-oxidation defect with detectable peroxisomes: a case with neonatal onset and progressive course. Eur J Pediatr 149: 722–726
Björkhem I, Sisfontes L, Boström B, Kase BF, Blomstrand R (1986) Simple diagnosis of the Zellweger syndrome by gasliquid chromatography of dimethylacetals. J Lipid Res 27: 786–791
Clayton PT, Lake BD, Hjelm M, Stephenson JBP, Besley GTN, Wanders RJA, Schram AW, Tager JM, Schutgens RBH, Lawson AM (1988) Bile acid analyses in “Pseudo-Zellweger” syndrome: clues to the defect in peroxisomal β-oxidation. J Inherited Metab Dis 11 [Suppl 2]: 165–168
Eldjarn L, Try K, Stokke O, Munthe Kaas AW, Refsum S, Steinberg O, Avigan J, Mize C (1966) Dietary effects of serum phytanic acid levels and on clinical manifestations in heredopathia atactica polyneuritiformis. Lancet I: 691
Goldfischer S, Collins J, Rapin I, Neumann P, Neglia W, Sprio AJ, Ishii T, Roels F, Vamecq J, Hoof F van (1986) Pseudo-Zellweger syndrome: deficiencies, in several peroxisomal oxidative activities. J Pediatr 108: 25–32
Heymans HSA, Wanders RJA, Schutgens RBH (1990) Peroxisomal Disorders. In: Fernandes J, Saudubray JM, Tada K (eds) Inborn metabolic diseases. Springer, Berlin Heidelberg New York, pp 421–433
Lazarow PB, Moser HW (1989) Disorders of peroxisome biogenesis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. Mc Graw-Hill, New York, pp 1479–1509
Monnens L, Heymans HSA (1987) Peroxisomal disorders: clinical characterization. J Inherited Metab Dis 10 [Suppl 1]: 23–32
Moser HW (1989) Peroxisomal diseases. Adv Pediatr 36: 1–38
Moser HW, Moser AB (1989) Adrenoleukodystrophy (x-linked). In: Scriver CR, Baudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 1511–1532
Moser HW, Moser AB, Kawamura N, Murphy J, Suzuki K, Schaumburg H, Kishimoto J (1980) Adrenoleukodystrophy: elevated C26 fatty acid in cultured skin fibroblasts. Ann Neurol 7: 542–549
Moser HW, Naidu S, Kumar AJ, Rosenbaum AE (1987) The adrenoleukodystrophies. CRC Crit Rev Neurobiol 3: 29–88
Palosaari PM, Hiltunen JK (1990) Peroxisomal bifunctional protein from rat liver is a trifunctional enzyme possessing 2-enoyl CoA hydratase, 3 hydroxyacyl-CoA dehydrogenase, and delta 3-delta 2-enoyl CoA isomerase activities. J Biol Chem 265: 2446–2449
Parmentier GP, Janssen GA, Eggermont EA, Eyssen HJ (1979) C27 bile acids in infants with coprostanoic acidemia and occurence of a 3α, 7α, 12α,-trihydroxy-5β-C29 dicarboxylic bile acid as a major component in their serum. Eur J Biochem 102: 173–183
Paturneau-Jouas F, Taillard F, Gansmuller A, Mikol J, Aigrot MS, Sereni C (1987) Clinical, biochemical and pathological aspects of a “Zellweger-like” peroxisomal disorder (abstract). In: R Salvayre (ed) Lipid storage disorders. Nato-Inserm, Toulouse, pp 133–134
Poll-Thé BT, Roels F, Ogier H, Scotto J, Vamecq J, Schutgens RBH, Wanders RJA, Roermund CWT van, Wijland MJA van, Schram AW, Tager JM, Saudubray JM (1988) A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). Am J Hum Genet 42: 422–434
Schrakamp G, Schalkwijk CG, Schutgens RBH, Wanders RJA, Tager JM, Bosch H van den (1988) Plasmalogen biosynthesis in peroxisomal disorders: fatty alcohol versus alkylglycerol precursors. J Lipid Res 29: 325–334
Schram AW, Goldfischer S, Roermund CWT van, Brouwer-Kelder EM, Collins J, Hashimoto T, Heymans HSA, Bosch H van den, Schutgens RBH, Tager JM, Wanders RJA (1987) Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. Proc Natl Acad Sci USA 84: 2494–2496
Suzuki Y, Shimozawa N, Orii T, Igarashi N, Kono N, Matsui A, Inoue Y, Yokata S, Hashimoto T (1988) Zellweger-like syndrome with detectable hepatic peroxisomes: a variant form of peroxisomal disorders. J Pediatr 113: 841–845
Wanders RJA, Heymans HSA, Schutgens RBH, Barth PG, Bosch H van den, Tager JM (1988) Peroxisomal disorders in neurology. J Neurol Sci 88: 1–39
Wanders RJA, Brink HJ ten, Roermund CW van, Schutgens RBH, Tager JM, Jacobs C (1990) Identification of pristanoyl-CoA oxidase activity in human liver and its deficiency in the Zellweger syndrome. Biochem Biophys Res Commun 172: 490–495
Wanders RJA, Roermund CWT van, Schutgens RBH, Barth PG, Heymans HSA, Bosch H van den, Tager JM (1990) The inborn errors of peroxisomal β-oxidation. J Inherited Metab Dis 13: 4–36
Wanders RJA, Roermund CWT van, Schelen A, Schutgens RBH, Tager JM, Stephenson JBP, Clayton PT (1990) A bifunctional protein with deficient enzymatic activity. Identification of a new peroxisomal disorders using novel methods to measure the peroxisomal β-oxidation enzyme activities. J Inherited Metab Dis 13: 375–379
Watkins PA, Mihalik SJ (1990) Mitochondrial oxidation of phytanic acid in human and monkey liver: implication that Refsum's disease is not a peroxisomal disorder. Biochem Biophys Res Commun 167: 580–586
Watkins PA, Chen WW, Harris CJ, Hoefler, G, Hoefler S, Blake DC Jr, Balfe A, Kelley RI, Moser AB, Beard ME, Moser HW (1989) Peroxisomal bifunctional enzyme deficiency. J Clin Invest 83: 771–777
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Santer, R., Claviez, A., Oldigs, H.D. et al. Isolated defect of peroxisomal β-oxidation in a 16-year-old patient. Eur J Pediatr 152, 339–342 (1993). https://doi.org/10.1007/BF01956749
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DOI: https://doi.org/10.1007/BF01956749