Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels
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Published:2022-12-05
Issue:1
Volume:17
Page:
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ISSN:1750-1172
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Container-title:Orphanet Journal of Rare Diseases
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language:en
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Short-container-title:Orphanet J Rare Dis
Author:
Shelkowitz Emily, Saneto Russell P., Al-Hertani Walla, Lubout Charlotte M. A., Stence Nicholas V., Brown Mark S., Long Patrick, Walleigh Diana, Nelson Julie A., Perez Francisco E., Shaw Dennis W. W., Michl Emma J., Van Hove Johan L. K.ORCID
Abstract
Abstract
Background
Nonketotic 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.
Aim
We aimed to assess clinical and biochemical effects of two glycine reduction strategies: high dose benzoate versus KD with low dose benzoate.
Methods
Six 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).
Results
Average 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.
Conclusion
KD 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.
Funder
NKH Crusaders Hope for NKH Foundation Brodyn's Friends Nora Jane Almany Foundation Dickens Family Foundation Les Petits Bourdons Lucas John Foundation Jacqueline Kirby Foundation University of Colorado Foundation
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics (clinical),General Medicine
Reference52 articles.
1. Van Hove J, Coughlin C II, Swanson M, Hennermann JB. Nonketotic hyperglycinemia. 2002 Nov 14 [Updated 2019 May 23]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2019. https://www.ncbi.nlm.nih.gov/books/NBK1357/. 2. Coughlin C II, Swanson MA, Kronquist K, Acquaviva C, Hutchin T, Rodriguez-Pombo P, et al. The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT. Genet Med. 2017;19:104–11. 3. Perry TL, Urquhart N, Maclean J, Evans ME, Hanson S, Davidson AGF, et al. Nonketotic hyperglycinemia: glycine accumulation due to absence of glycine cleavage in the brain. N Engl J Med. 1975;292:1269–73. 4. Hennermann JB, Berger JM, Grieben U, Scharer G, Van Hove JLK. Prediction of long-term outcome in glycine encephalopathy: a clinical survey. J Inherit Metab Dis. 2012;35(2):253–61. 5. Swanson MA, Coughlin CR II, Scharer GH, Szerlong HJ, Bjoraker KJ, Spector EB, et al. Biochemical and molecular predictors of prognosis in nonketotic hyperglycinemia. Ann Neurol. 2015;78:606–18.
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