European Journal of Pediatrics

, Volume 149, Issue 10, pp 709–712 | Cite as

Recurrent, familial Reye-like syndrome with a new complex amino and organic aciduria

  • O. N. Elpeleg
  • E. Christensen
  • H. Hurvitz
  • D. Branski
Metabolic Diseases


Five of 13 siblings from a Jewish-Ashkenazi family suffered from recurrent Reye-like episodes. During attacks, these patients excreted α-keto-adipic, α-hydroxy-adipic, and α-aminoadipic acids, branched-chain keto acids and saccharopine in addition, to lactic, pyruvic, and dicarboxylic acids characteristic of Reye syndrome. The serum concentrations of citrulline and α-aminoadipic acid were elevated and carnitine was at the upper limit of the normal range. Serum acetoacetate level was 4–5 times the β-hydroxybutyrate level, but the pyruvate/lactate ratio was normal. Notably, plasma ketone bodies were lower than expected from the degree of catabolism. When the patients were symptom-free, no abnormal amino or organic acids in serum or urine were detected. These findings might be interpreted as a functional impairment at three different biochemical sites: fatty acid β-oxidation, dehydrogenase complexes of the pyruvic, α-ketoglutaric, α-ketoadipic, and branched-chain keto acids, and pyruvate carboxylase. We suggest that in this hereditary disorder a toxic substance, exogenously or endogenously derived, interfered at multiple sites in different metabolic pathways.

Key words

Reye-like syndrome Organic acids Amino acids 


A/B ratio

acetoacetate/3-hydroxybutyrate ratio


Reye syndrome


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Applegarth DA, Edelsten AD, Wong TLK, Morrison BJ (1979) Observed range of assay values for plasma and cerebrospinal fluid amino acid levels in infants and children aged 3 months to 10 years. Clin Biochem 12: 173–178CrossRefPubMedGoogle Scholar
  2. 2.
    Brown T, Hug G, Lanski L, Bove K, Scheve A, Ryan M, Brown H, Schubert WK, Partin JC, Lloyd-Still J (1976) Transiently reduced activity of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome. N Engl J Med 294: 861–867PubMedGoogle Scholar
  3. 3.
    Christensen E (1987) HPLC analysis of physiological amino acids as their phenylthiocarbamyl derivatives. The Society for the Study of Inborn Errors of Metabolism, Sheffield, UK, 25th Annual Symposium, 22–25 September 1987, p 66Google Scholar
  4. 4.
    Christensen E, Brock Jacobsen B, Gregersen N, Hjeds H, Pedersen JB, Brandt NJ, Baekmark UB (1981) Urinary excretion of succinylacetone and δ-aminolevulinic acid in patients with hereditary tyrosinemia. Clin Chim Acta 116:331–341CrossRefPubMedGoogle Scholar
  5. 5.
    Christensen E, Kolvraa S, Gregersen N (1984) Glutaric aciduria type II: evidence for a defect related to the electron transfer flavoprotein or its dehydrogenase. Pediatr Res 18: 663–667PubMedGoogle Scholar
  6. 6.
    Coates PM, Hale DE, Stanley CA, Corkey BE, Cortner JA (1985) Genetic deficiency of medium-chain acyl coenzyme A dehydrogenase: studies in cultured skin fibroblasts and peripheral mononuclear leukocytes. Pediatr Res 19: 671–676PubMedGoogle Scholar
  7. 7.
    Haymond MW, Karl IE, Keating JP, DeVivo D (1978) Metabolic response to hypertonic glucose administration in Reye syndrome. Ann Neurol 3: 207–215CrossRefPubMedGoogle Scholar
  8. 8.
    Reye RDK, Morgan G, Baral J (1963) Encephalopathy and fatty degeneration of the viscera a disease entity in childhood Lancet II: 749–752CrossRefGoogle Scholar
  9. 9.
    Robinson BH, Gall DG, Cutz E (1977) Deficient activity of hepatic pyruvate dehydrogenase and pyruvate carboxylase in Reye's syndrome. Pediatr Res 11: 279–281PubMedGoogle Scholar
  10. 10.
    Sakaguchi Y, Yoshino M, Yoshida I, Yamashita F, Kuhara T, Matsumoto I, Hayashi T (1986) Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction. Eur J Pediatr 145: 271–274CrossRefPubMedGoogle Scholar
  11. 11.
    Snodgrass PJ, Delong GR (1976) Urea cycle enzyme deficiencies and an increased nitrogen load producing hyperammonemia in Reye's syndrome. N Engl J Med 294: 855–860PubMedGoogle Scholar
  12. 12.
    Yoshida Y, Fujii M, Brown III FR, Sngh I (1988) Effect of salicylic acid on mitochondrial-peroxisomal fatty acid catabolism. Pediatr Res 23: 338–341PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • O. N. Elpeleg
    • 1
  • E. Christensen
    • 2
  • H. Hurvitz
    • 3
  • D. Branski
    • 3
  1. 1.Metabolic LaboratoryShaare-Zedek HospitalJerusalemIsrael
  2. 2.The Section of Clinical Genetics, Metabolic LaboratoryRigshospitaletCopenhagenDenmark
  3. 3.Department of PaediatricsBikur-Cholim HospitalJerusalemIsrael

Personalised recommendations