Benzoate treatment and the glycine index in nonketotic hyperglycinaemia
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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.
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- Benzoate treatment and the glycine index in nonketotic hyperglycinaemia
Journal of Inherited Metabolic Disease
Volume 28, Issue 5 , pp 651-663
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- 1. Department of Pediatrics, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium
- 2. Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA
- 7. Biochemical Genetics Laboratory, University of Colorado Health Sciences Center at Fitzsimmons, Mailstop 8313, PO Box 6511, Aurora, CO, 80045-0511, USA
- 3. Department of Nutrition, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium
- 4. Otto-Heubner-Center for Pediatric and Adolescent Medicine, Charité University Medical Center, Berlin, Germany
- 5. Department of Laboratory Medicine, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium
- 6. Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA