Intravenous ketogenic diet therapy for neonatal-onset pyruvate dehydrogenase complex deficiency.

Abstract

BACKGROUND:

Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that causes lactic acidosis and neurodevelopmental changes. Five causative genes have been identified: PDHA1, PDHB, DLAT, DLD, and PDHX. Four neurological phenotypes have been reported: neonatal encephalopathy with lactic acidosis, non-progressive infantile encephalopathy, Leigh syndrome, and relapsing ataxia. Of these, neonatal encephalopathy has the worst mortality and morbidity and there is no effective treatment.

SUBJECTS AND METHODS:

We studied two girls who were clinically diagnosed with PDHC deficiency as neonates; they were subsequently found to have PDHA1 mutations. The clinical diagnosis was based on white matter loss and a lateral ventricular septum on fetal MRI, spasticity of the lower extremities, and lactic acidosis worsening after birth. Intravenous ketogenic diets were started within 24 h after birth. The ketogenic ratio was increased until the blood lactate level was controlled, while monitoring for side effects.

RESULTS:

In both cases, the lactic acidosis improved immediately with no apparent side effects. Both children had better developmental outcomes than previously reported cases; neither exhibited epilepsy.

CONCLUSIONS:

Intravenous ketogenic diet therapy is a treatment option for neonatal-onset PDHC deficiency. Further studies are needed to optimize this therapy.

• Authors: Takehiko Inui, Yoichi Wada, Moriei Shibuya, Natsuko Arai-Ichinoi, Yukimune Okubo, Wakaba Endo, Toshihiko Uchida, Noriko Togashi, Etsuo Naito, Kazuhiro Haginoya
• Journal: Brain & development (Brain Dev) Vol. 44 Issue 3 Pg. 244-248 (Mar 2022) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 34863613 (Publication Type: Case Reports)
• Copyright: Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Topics

• Diet, Ketogenic
• Female
• Humans
• Infant
• Infant, Newborn
• Parenteral Nutrition
• Pyruvate Dehydrogenase Complex Deficiency Disease (diet therapy)