Advertisement

Nonketotic Hyperglycinemia

A Paradigm for the Application of Neuroscience to the Understanding and Treatment of a Developmental Disorder
  • Stephen I. Deutsch
  • Lynn H. Deutsch
  • Ronit Weizman

Abstract

Nonketotic hyperglycinemia is an autosomal-recessive disorder that usually presents during the neonatal period and, in its classic or typical form, is characterized by poor muscle tone, feeding difficulties, intractable seizures, and death due to respiratory insufficiency.1,2 Phenotypically, the disorder can be quite heterogeneous; atypical presentations include mild mental retardation and expressive language difficulties as the sole features.3-8 In many ways, nonketotic hyperglycinemia serves as a paradigm for the application of basic neuroscience to the understanding and treatment of a developmental disorder.

Keywords

Sodium Benzoate Classic Presentation Glycine Level Glycine Cleavage System Nonketotic Hyperglycinemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ziter FA, Bray PF, Madsen JA, et al : The clinical findings in a patient with non-ketotic hyperglycinemia. Pediatr Res 2:250–253, 1968PubMedCrossRefGoogle Scholar
  2. 2.
    Perry TL, Urquhart N, MacLean J, et al : Nonketotic hyperglycinemia. Glycine accumulation due to absence of glycine cleavage in brain. N Engl J Med 292:1269–1273, 1975PubMedCrossRefGoogle Scholar
  3. 3.
    Bank WJ, Morrow G III : A familial spinal cord disorder with hyperglycinemia. Arch Neurol 27:136–144, 1972PubMedCrossRefGoogle Scholar
  4. 4.
    Holmgren G, son Blomquist HK : Non-ketotic hyperglycinemia in two sibs with mild psycho-neurological symptoms. Neuropadiatrie 8:67–72, 1977PubMedCrossRefGoogle Scholar
  5. 5.
    Frazier DM, Summer GK, Chamberlin HR : Hyperglycinuria and hyperglycinemia in two siblings with mild developmental delays. Am J Dis Child 132:777–781, 1978PubMedGoogle Scholar
  6. 6.
    Ando T, Nyhan WL, Bicknell J, et al : Non-ketotic hyperglycinaemia in a family with an unusual phenotype. J Inher Metab Dis 1:79–83, 1978PubMedCrossRefGoogle Scholar
  7. 7.
    Flannery DB, Pellock J, Bousounis D, et al : Nonketotic hyperglycinemia in two retarded adults: A mild form of infantile nonketotic hyperglycinemia. Neurology (NY) 33:1064–1066, 1983Google Scholar
  8. 8.
    Cole DEC, Meek DC : Juvenile non-ketotic hyperglycinaemia in three siblings. J Inher Metab Dis 8(suppl 2): 123–124, 1985PubMedCrossRefGoogle Scholar
  9. 9.
    Ando T, Nyhan WL, Gerritsen T, et al : Metabolism of glycine in the nonketotic form of hyperglycinemia. Pediatr Res 2:254–263, 1968PubMedCrossRefGoogle Scholar
  10. 10.
    DeGroot CJ, Troelstra JA, Hommes FA : Nonketotic hyperglycinemia: An in vitro study of the glycineserine conversion in liver of three patients and the effect of dietary methionine. Pediatr Res 4:238–243, 1970CrossRefGoogle Scholar
  11. 11.
    Spielberg SP, Lucky AW, Schulman JD, et al: Failure of leucovorin therapy in nonketotic hyperglycinemia. J Pediatr 89:681, 1976CrossRefGoogle Scholar
  12. 12.
    Krieger I, Winbaum ES, Eisenbrey AB : Cerebrospinal fluid glycine in nonketotic hyperglycinemia. Effect of treatment with sodium benzoate and a ventricular shunt. Metabolism 26:517–524, 1977PubMedCrossRefGoogle Scholar
  13. 13.
    Gitzelmann R, Steinmann B, Otten A, et al : Nonketotic hyperglycinemia treated with strychnine, a glycine receptor antagonist. Helv Paediatr Acta 32:517–525, 1977Google Scholar
  14. 14.
    Ameson D, Ch’ien LT, Chance P, et al: Strychnine therapy in nonketotic hyperglycinemia. Pediatrics 63:369–373, 1979Google Scholar
  15. 15.
    Steinmann B, Gitzelmann R : Strychnine treatment attempted in newborn twins with severe nonketotic hyperglycinemia. Helv Paediatr Acta 34:589–599, 1979PubMedGoogle Scholar
  16. 16.
    Melancon SB, Dallaire L, Vincelette P, et al: Early treatment of severe infantile glycine encephalopathy (nonketotic hyperglycinemia) with strychnine and sodium benzoate. Prog Clin Biol Res 34:217–229, 1979PubMedGoogle Scholar
  17. 17.
    von Wendt L, Simila S, Saukkonen A-L, et al : Failure of strychnine treatment during the neonatal period in three Finnish children with nonketotic hyperglycinemia. Pediatrics 65:1166–1169, 1980Google Scholar
  18. 18.
    MacDermot KD, Nelson W, Reichert CM, et al : Attempts at use of strychnine sulfate in the treatment of nonketotic hyperglycinemia. Pediatrics 65:61–64, 1980PubMedGoogle Scholar
  19. 19.
    Warburton D, Boyle RJ, Keats JP, et al : Nonketotic hypreglycinemia. Effects of therapy with strychnine. Am J Dis Child 134:273–275, 1980PubMedGoogle Scholar
  20. 20.
    Matalon R, Michals K, Naidu S, et al : Treatment of non-ketotic hyperglycinaemia with diazepam, choline and folic acid. J Inher Metab Dis 5(suppl 1):3–5, 1982CrossRefGoogle Scholar
  21. 21.
    Matalon R, Naidu S, Hughes JR, et al : Nonketotic hyperglycinemia: Treatment with diazepam— A competitor for glycine receptors. Pediatrics 71:581–584, 1983PubMedGoogle Scholar
  22. 22.
    Wolff JA, Kulovich S, Yu AL, et al : The effectiveness of benzoate in the management of seizures in nonketotic hyperglycinemia. Am J Dis Child 140:596–602, 1986PubMedGoogle Scholar
  23. 23.
    Haan EA, Kirby DM, Tada K, et al : Difficulties in assessing the effect of strychnine on the outcome of nonketotic hyperglycinaemia. Observations on sisters with a mild T-protein defect. Eur J Pediatr 145:267–270, 1986PubMedCrossRefGoogle Scholar
  24. 24.
    Young AB, Snyder SH : Strychnine binding in rat spinal cord membranes associated with the synaptic glycine receptor: Cooperativity of glycine interactions. Mol Pharmacol 10:790–809, 1974Google Scholar
  25. 25.
    Synder SH : The glycine synaptic receptor in the mammalian central nervous system. Br J Pharmacol 53:473–484, 1975Google Scholar
  26. 26.
    Grenningloh G, Rienitz A, Schmitt B, et al : The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature (Lond) 328:215–220, 1987CrossRefGoogle Scholar
  27. 27.
    Ascher P, Nowak L : Electrophysiological studies of NMDA receptors. Trends Neurosci 10:284–288, 1987CrossRefGoogle Scholar
  28. 28.
    Cotman CW, Iversen LL : Excitatory amino acids in the brain-focus on NMDA receptors. Trends Neurosci 10:263–265, 1987CrossRefGoogle Scholar
  29. 29.
    Kemp JA, Foster AC, Wong EHF : Non-competitive antagonists of excitatory amino acid receptors. Trends Neurosci 10:294–298, 1987CrossRefGoogle Scholar
  30. 30.
    Hayasaka K, Tada K, Kikuchi G, et al : Nonketotic hyperglycinemia: Two patients with primary defects of Pprotein and T-protein, respectively, in the glycine cleavage system. Pediatr Res 17:967–970, 1983PubMedCrossRefGoogle Scholar
  31. 31.
    Hayasaka K, Tada K, Fueki N, et al : Nonketotic hyperglycinemia: Analyses of glycine cleavage system in typical and atypical cases. J Pediatr 110:873–877, 1987PubMedCrossRefGoogle Scholar
  32. 32.
    Young AB, Zukin SR, Snyder SH : Interaction of benzodiazepines with central nervous glycine receptors: Possible mechanism of action. Proc Natl Acad Sci USA 71:2246–2250, 1974PubMedCrossRefGoogle Scholar
  33. 33.
    Mohler H, Okada T : Benzodiazepine receptor: Demonstration in the central nervous system. Science 198:849–851, 1977PubMedCrossRefGoogle Scholar
  34. 34.
    Squires RF, Braestrup C : Benzodiazepine receptors in rat brain. Nature (Lond) 266:732–734, 1977CrossRefGoogle Scholar
  35. 35.
    Olsen RW : GABA-benzodiazepine barbiturate receptor interactions. J Neurochem 37:1–13, 1981PubMedCrossRefGoogle Scholar
  36. 36.
    Jones EG : Neurotransmitters in the cerebral cortex. J Neurosurg 65:135–153, 1986PubMedCrossRefGoogle Scholar
  37. 37.
    DeGroot CJ, Boeli Everts V, Touwen BCL, et al : Non-ketotic hyperglycinemia (NKH): An inborn error of metabolism affecting brain function exclusively. Prog Brain Res 48:199–207, 1978CrossRefGoogle Scholar
  38. 38.
    Benavides J, Lopez-Lahoya J, Valdivieso F, et al : Postnatal development of synaptic glycine receptors in normal and hyperglycinemic rats. J Neurochem 37:315–320, 1981PubMedCrossRefGoogle Scholar
  39. 39.
    von Wendt L : Experimental hyperglycinaemia— An evaluation of the efficacy of strychnine therapy in nonketotic hyperglycinaemia. J Ment Defic Res 23:195–205, 1979Google Scholar
  40. 40.
    von Wendt L, Simila S, Saukkonen A-L, et al : Prenatal brain damage in nonketotic hyperglycinemia. Am J Dis Child 135:1072, 1981Google Scholar
  41. 41.
    Trauner DA, Page T, Greco C, et al : Progressive neurodegenerative disorder in a patient with nonketotic hyperglycinemia. J Pediatr 98:272–275, 1981PubMedCrossRefGoogle Scholar
  42. 42.
    Dobyns WB : Agenesis of the corpus callosum and gyral malformations are frequent manifestations of nonketotic hyperglycinemia. Neurology 39:817–820, 1989PubMedGoogle Scholar
  43. 43.
    Press GA, Barshop BA, Haas RH, et al : Abnormalities of the brain in nonketotic hyperglycinemia: MR manifestations. AJNR 10(2)315–321, 1989PubMedGoogle Scholar
  44. 44.
    Singer HS, Valle D, Hayasaka K, et al : Nonketotic hyperglycinemia: Studies in an atypical variant. Neurology 39:286–288, 1989PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Stephen I. Deutsch
    • 1
  • Lynn H. Deutsch
    • 1
  • Ronit Weizman
    • 2
    • 3
  1. 1.Psychiatry Service, Veterans Administration Medical Center, and Department of PsychiatryGeorgetown University School of MedicineUSA
  2. 2.Pediatric DepartmentHasharon HospitalPetah TiqvaIsrael
  3. 3.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Personalised recommendations