Systematic Reviews
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Pediatr. Dec 9, 2023; 12(5): 350-358
Published online Dec 9, 2023. doi: 10.5409/wjcp.v12.i5.350
Warburg effect mimicking inborn errors of metabolism in childhood hematologic malignancies: A case-based systematic review
Khanittha Permtawee, Maliwan Tengsujaritkul, Chane Choed-Amphai, Supapitch Chanthong, Kanittha Mankhemthong, Lalita Sathitsamitphong, Rungrote Natesirinilkul, Pimlak Charoenkwan
Khanittha Permtawee, Maliwan Tengsujaritkul, Chane Choed-Amphai, Supapitch Chanthong, Lalita Sathitsamitphong, Rungrote Natesirinilkul, Pimlak Charoenkwan, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
Kanittha Mankhemthong, Department of Pediatrics, Nakornping Hospital, Chiang Mai 50180, Thailand
Author contributions: Permtawee K, Tengsujaritkul M and Choed-Amphai C drafted the manuscript; Permtawee K, Tengsujaritkul M, Choed-Amphai C, Chanthong S, Mankhemthong K, Sathitsamitphong L, Natesirinilkul R and Charoenkwan P participated in patient management and data collection; Permtawee K, Choed-Amphai C and Chanthong S contributed to the systematic review; All authors contributed to the article and approved the submitted version.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chane Choed-Amphai, MD, Doctor, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, No. 110 Intawarorot road, Sriphum, Muang, Chiang Mai 50200, Thailand. chane.c@cmu.ac.th
Received: July 22, 2023
Peer-review started: July 22, 2023
First decision: September 4, 2023
Revised: September 9, 2023
Accepted: September 26, 2023
Article in press: September 26, 2023
Published online: December 9, 2023
Processing time: 139 Days and 0.1 Hours
Abstract
BACKGROUND

Type B lactic acidosis and hypoglycemia can occur in various pediatric conditions. In young children with a history of fasting preceding these metabolic derangements, inborn errors of metabolism should be primarily considered. However, the Warburg effect, a rare metabolic complication, can also manifest in children with hematologic malignancies. Only a few reports of this condition in children have been published in the literature.

AIM

To identify the clinical course, treatment strategies, and outcomes of childhood hematologic malignancies with type B lactic acidosis.

METHODS

We performed a comprehensive search of the PubMed, Scopus, and Cochrane databases without any time restriction but limited to English language articles. The databases were last accessed on July 1st, 2023.

RESULTS

A total of 20 publications were included in the analysis, all of which were case reports or case series. No higher quality evidence was available. Among children with hematologic malignancies and Warburg effect, there were 14 cases of acute lymphoblastic leukemia and 6 cases of non-Hodgkin’s lymphoma including our illustrative case. Lactic acidosis occurred in 55% of newly diagnosed cases and 45% of relapsed cases. The mean age was 10.3 ± 4.5 years, and 80% of cases were male. The mean serum lactate was 16.9 ± 12.6 mmol/L, and 43.8% of the cases had concomitant hypoglycemia. Lactic acidosis initially subsided in 80% of patients receiving chemotherapy compared to 60% in the contrast group. The mortality rate of newly diagnosed cases was 45.5%, while the relapsed cases represented a 100% mortality rate. All 8 patients reported before 2001 died from disease-related complications. However, patients described in reports published between 2003 and 2023 had a 54.5% rate of complete remission.

CONCLUSION

This complication has historically led to fatal outcome; however, patients who received chemotherapy showed a more favorable response. Therefore, it is crucial to promptly initiate specific treatment in this context.

Keywords: Warburg effect, Lactic acidosis type B, Inborn errors of metabolism, Leukemia, Lymphoma, Children

Core Tip: In children with a history of fasting preceding lactic acidosis, inborn errors of metabolism (IEM) should be considered. However, we describe a case of 10-year-old boy with Burkitt leukemia who exhibited Warburg effect mimicking IEM. The most recent review on lactic acidosis in pediatric leukemia/lymphoma was published in the journal Cancer in 2001. All cases published to that date experienced worsening or recurrence of lactic acidosis, with a mortality rate of 100%. However, this updated systematic review has shown improved outcomes for children with this complication over the past two decades. Newly diagnosed patients and those who received chemotherapy displayed more favorable outcomes.