Journal of Inherited Metabolic Disease

, Volume 28, Issue 5, pp 651–663 | Cite as

Benzoate treatment and the glycine index in nonketotic hyperglycinaemia

  • J. L. K. Van Hove
  • K. Vande Kerckhove
  • J. B. Hennermann
  • V. Mahieu
  • P. Declercq
  • S. Mertens
  • M. De Becker
  • P. S. Kishnani
  • J. Jaeken


High-dose benzoate treatment aimed at reducing plasma glycine levels to normal reduces seizures and increases wakefulness in patients with nonketotic hyperglycinaemia (NKH). Since benzoate metabolism is dependent on the available glycine pool, and since the glycine pool is variably affected by the deficiency in the glycine cleavage enzyme system, we examined the importance of interpatient variability in benzoate requirement. To correct for the dietary glycine contribution, the glycine index was introduced as the molar requirement of benzoate dose necessary to normalize plasma glycine levels and subtracting from that the dietary glycine intake, both corrected for weight. The glycine index varied between 3.62 and 4.87 mmol/kg per day in five patients with a poor neurodevelopmental outcome and between 0.92 and 1.90 mmol/kg per day in four patients with a better neurodevelopmental outcome, and was 2.54 mmol/kg per day in a single patient with an intermediate outcome. The glycine index was stable over time within each patient. Exceeding the balance by either increasing food glycine intake or decreasing the benzoate dose resulted in increased glycine levels. Exceeding the glycine tolerance by increasing benzoate resulted in elevated and toxic levels of benzoate. The glycine index is a stable, individually specific parameter in patients with NKH. It has clinical consequences for the dose of benzoate required and the role of dietary management. Through its correlation with neurodevelopmental outcome, the glycine index points to potential genetic factors that could contribute to the psychomotor retardation in NKH.


Glycine Intermediate Outcome Cleavage Enzyme Index Point Psychomotor Retardation 
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.


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Copyright information

© SSIEM and Springer 2005

Authors and Affiliations

  • J. L. K. Van Hove
    • 1
    • 2
    • 7
  • K. Vande Kerckhove
    • 3
  • J. B. Hennermann
    • 4
  • V. Mahieu
    • 1
  • P. Declercq
    • 5
  • S. Mertens
    • 1
  • M. De Becker
    • 1
  • P. S. Kishnani
    • 6
  • J. Jaeken
    • 1
  1. 1.Department of Pediatrics, University Hospital GasthuisbergKatholieke Universiteit LeuvenBelgium
  2. 2.Department of PediatricsUniversity of Colorado Health Sciences CenterDenverUSA
  3. 3.Department of Nutrition, University Hospital GasthuisbergKatholieke Universiteit LeuvenBelgium
  4. 4.Otto-Heubner-Center for Pediatric and Adolescent MedicineCharité University Medical CenterBerlinGermany
  5. 5.Department of Laboratory Medicine, University Hospital GasthuisbergKatholieke Universiteit LeuvenBelgium
  6. 6.Department of Pediatrics, Division of Medical GeneticsDuke University Medical CenterDurhamUSA
  7. 7.Biochemical Genetics LaboratoryUniversity of Colorado Health Sciences Center at FitzsimmonsAuroraUSA

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