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Neuropediatrics 2022; 53(01): 065-068
DOI: 10.1055/s-0041-1732446
Short Communication

Ketogenic Diet for KARS-Related Mitochondrial Dysfunction and Progressive Leukodystrophy

Yuka Murofushi 
1   Division of Neurology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
,
Itaru Hayakawa
1   Division of Neurology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
,
Yuichi Abe
1   Division of Neurology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
,
Tatsuyuki Ohto
2   Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
,
Kei Murayama
3   Center for Medical Genetics, Department of Metabolism, Chiba Children's Hospital, Midori-ku, Chiba, Japan
,
Hisato Suzuki 
4   Center for Medical Genetics, Keio University Hospital, Shinjuku-ku, Tokyo, Japan
,
Toshiki Takenouchi
4   Center for Medical Genetics, Keio University Hospital, Shinjuku-ku, Tokyo, Japan
,
Kenjiro Kosaki
4   Center for Medical Genetics, Keio University Hospital, Shinjuku-ku, Tokyo, Japan
,
Masaya Kubota 
1   Division of Neurology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
› Author Affiliations Funding This work was supported in part by the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED (JP19ek0109273, JP20ek0109468) to K.M. and (JP19ek0109301) to K.K. (http://www.amed.go.jp/en/). This study was approved by the Institutional Review Board at the National Center for Child Health and Development (#2020-068).
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Abstract

KARS encodes lysyl-tRNA synthetase, which is essential for protein translation. KARS mutations sometimes cause impairment of cytoplasmic and mitochondrial protein synthesis, and sometimes lead to progressive leukodystrophies with mitochondrial signature and psychomotor regression, and follow a rapid regressive course to premature death. There has been no disease-modifying therapy beyond supportive treatment. We present a 5-year-old male patient with an asymmetrical leukodystrophy who showed overt evidence of mitochondrial dysfunction, including elevation of lactate on brain MR spectroscopy and low oxygen consumption rate in fibroblasts. We diagnosed this patient's condition as KARS-related leukodystrophy with cerebral calcification, congenital deafness, and evidence of mitochondrial dysfunction. We employed a ketogenic diet as well as multiple vitamin supplementation with the intention to alleviate mitochondrial dysfunction. The patient showed alleviation of his psychomotor regression and even partial restoration of his abilities within 4 months. This is an early report of a potential disease-modifying therapy for KARS-related progressive leukodystrophy without appreciable adverse effects.

Keywords

KARS - progressive leukodystrophy - psychomotor regression - mitochondrial dysfunction - ketogenic diet - vitamin supplementation

Supplementary Material



Publication History

Received: 22 November 2020

Accepted: 10 June 2021

Article published online:
26 August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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