Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels

Orphanet Journal of Rare Diseases

Research

Francisco E. Perez¹  Dennis W. W. Shaw¹  Nicholas V. Stence²  Mark S. Brown²  Walla Al-Hertani³  Emma J. Michl³  Russell P. Saneto⁴  Julie A. Nelson⁵  Diana Walleigh⁵  Patrick Long⁶  Emily Shelkowitz⁶  Johan L. K. Van Hove⁶  Charlotte M. A. Lubout⁷ 

[1] Department of Radiology, Seattle Children’s Hospital, University of Washington, Seattle, WA, USA;Department of Radiology, University of Colorado, Aurora, CO, USA;Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA;Division of Pediatric Neurology, Department of Neurology, Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle Children’s Hospital, 98105, Seattle, WA, USA;Section of Child Neurology, Department of Pediatrics, University of Colorado, Aurora, CO, USA;Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Education 2 South, L28-4114, East 17Th Avenue, 80045, Aurora, CO, USA;Section of Metabolic Diseases, Beatrix Children’s Hospital, University of Groningen, University Medical Center, Groningen, Groningen, The Netherlands;

关键词: Nonketotic hyperglycinemia;    Benzoate;    Ketogenic diet;    Magnetic resonance spectroscopy;    Glycine;    Epilepsy;   

DOI  :  10.1186/s13023-022-02581-6

 received in 2022-08-26, accepted in 2022-11-20,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundNonketotic hyperglycinemia (NKH) is a severe neurometabolic disorder characterized by increased glycine levels. Current glycine reduction therapy uses high doses of sodium benzoate. The ketogenic diet (KD) may represent an alternative method of glycine reduction.AimWe aimed to assess clinical and biochemical effects of two glycine reduction strategies: high dose benzoate versus KD with low dose benzoate.MethodsSix infants with NKH were first treated with high dose benzoate therapy to achieve target plasma glycine levels, and then switched to KD with low dose benzoate. They were evaluated as clinically indicated by physical examination, electroencephalogram, plasma and cerebral spinal fluid amino acid levels. Brain glycine levels were monitored by magnetic resonance spectroscopy (MRS).ResultsAverage plasma glycine levels were significantly lower with KD compared to benzoate monotherapy by on average 28%. Two infants underwent comparative assessments of brain glycine levels via serial MRS. A 30% reduction of brain glycine levels was observed in the basal ganglia and a 50% reduction in the white matter, which remained elevated above normal, and was equivalent between the KD and high dose benzoate therapies. CSF analysis obtained while participants remained on the KD showed a decrease in glycine, serine and threonine levels, reflecting their gluconeogenetic usage. Clinically, half the patients had seizure reduction on KD, otherwise the clinical impact was variable.ConclusionKD is an effective glycine reduction method in NKH, and may provide a more consistent reduction in plasma glycine levels than high-dose benzoate therapy. Both high-dose benzoate therapy and KD equally reduced but did not normalize brain glycine levels even in the setting of low-normal plasma glycine.

【 授权许可】

CC BY   
© The Author(s) 2022

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