Leigh syndrome-like MRI changes in a patient with biallelic HPDL variants treated with ketogenic diet

Yurika Numata-Uematsu; Mitsugu Uematsu; Toshiyuki Yamamoto; Hirotomo Saitsu; Yu Katata; Yoshitsugu Oikawa; Naoya Saijyo; Takehiko Inui; Kei Murayama; Akira Ohtake; Hitoshi Osaka; Jun-Ichi Takanashi; Shigeo Kure; Ken Inoue

doi:10.1016/j.ymgmr.2021.100800

Leigh syndrome-like MRI changes in a patient with biallelic HPDL variants treated with ketogenic diet

Mol Genet Metab Rep. 2021 Sep 4:29:100800. doi: 10.1016/j.ymgmr.2021.100800. eCollection 2021 Dec.

Authors

Affiliations

¹ Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
² Institute of Medical Genetics, Tokyo Women's Medical University; Tokyo Women's Medical University Institute of Integrated Medical Sciences, Tokyo, Japan.
³ Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
⁴ Department of Pediatric Neurology, Miyagi Children's Hospital, Sendai, Japan.
⁵ Center for Medical Genetics and Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
⁶ Department of Pediatrics & Clinical Genomics, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
⁷ Center for Intractable Diseases, Saitama Medical University Hospital, Saitama, Japan.
⁸ Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
⁹ Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan.
¹⁰ Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

Abstract

Biallelic 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) variants were recently reported as a cause of progressive and incurable neurodegenerative diseases ranging from neonatal-onset leukoencephalopathy with severe neurodevelopmental delay to spastic paraplegia. Although the physiological function of HPDL remains unknown, its subcellular localization in the mitochondria has been reported. Here, we report a case of HPDL-related neurological disease that was clinically and neuroimaging compatible with Leigh syndrome, previously unreported, and was treated with a ketogenic diet.

Keywords: HPDL; HPDL, 4-hydroxyphenylpyruvate dioxygenase-like protein; Ketogenic diet; LS, Leigh syndrome; Leigh syndrome; Leukoencephalopathy; MRS, Magnetic resonance spectroscopy; Mitochondria; PDHC, Pyruvate dehydrogenase complex.