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Licensed Unlicensed Requires Authentication Published by De Gruyter October 9, 2020

Characterization and outcome of 11 children with non-diabetic ketoacidosis

Elsayed Abdelkreem ORCID logo, Rofaida M. Magdy and Abdelrahim A. Sadek

Abstract

Objectives

To study the clinical and laboratory features, management, and outcome of pediatric non-diabetic ketoacidosis (NDKA).

Methods

Between May 2018 and April 2020, we prospectively collected children under 18 years who presented with ketoacidosis, defined as ketosis (urinary ketones ≥++ and/or serum β-hydroxybutyrate level ≥3 mmol/L) and metabolic acidosis (pH <7.3 and HCO3 <15 mmol/L). Children with HbA1c level ≥6.5% at initial presentation and those meeting the diagnostic criteria for DM during follow-up were excluded. Data were collected on demographics, clinical and laboratory features, management, and outcome.

Results

Eleven children with 19 episodes of NDKA were identified. The median age was 12 months (range from 5 months to 5 years). They manifested dehydration and disturbed conscious level (all cases), convulsions (n=6), hypoglycemia (n=6), hyperglycemia (n=2) and significant hyperammonemia (n=4). Most cases required intensive care management. Death or neurodevelopmental impairment occurred in six cases. Seven cases had inborn errors of metabolism (IEMs). Other cases were attributed to starvation, sepsis, and salicylate intoxication.

Conclusions

This is the largest case series of pediatric NDKA. Ketoacidosis, even with hyperglycemia, is not always secondary to diabetes mellitus. IEMs may constitute a significant portion of pediatric NDKA. Increased awareness of this unfamiliar condition is important for prompt diagnosis, timely management, and better outcome.


Corresponding author: Elsayed Abdelkreem, MD, PhD, Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag 82524, Egypt, E-mail:

Acknowledgments

The authors would like to appreciate the invaluable inputs from Prof. Toshiyuki Fukao (Gifu University, Japan) during study design and implementation. Prof. Fukao died at the beginning of 2020. He had a long-term and considerable contribution to scientific research, particularly in the field of ketone body metabolism and its defects.

  1. Research funding: None declared.

  2. Author contributions: Elsayed Abdelkreem conceived and designed the study, shared in data collection, and wrote the first draft of the manuscript. Rofaida M. Magdy was involved in clinical management and follow up of patients, shared in data collection, and revised manuscript. Abdelrahim A. Sadek supervised the whole study and critically revised the manuscript. All authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board approved this study.

References

1. Morton, A. Review article: ketoacidosis in the emergency department. Emerg Med Australas 2020;32:371–6. https://doi.org/10.1111/1742-6723.13503.Search in Google Scholar PubMed

2. Cartwright, MM, Hajja, W, Al-Khatib, S, Hazeghazam, M, Sreedhar, D, Li, RN, et al. Toxigenic and metabolic causes of ketosis and ketoacidotic syndromes. Crit Care Clin 2012;28:601–31. https://doi.org/10.1016/j.ccc.2012.07.001.Search in Google Scholar PubMed

3. Fukao, T, Mitchell, G, Sass, JO, Hori, T, Orii, K, Aoyama, Y. Ketone body metabolism and its defects. J Inherit Metab Dis 2014;37:541–51. https://doi.org/10.1007/s10545-014-9704-9.Search in Google Scholar PubMed

4. Bai, K, Fu, Y, Liu, C, Xu, F, Zhu, M. Pediatric non-diabetic ketoacidosis: a case-series report. BMC Pediatr 2017;17:209. https://doi.org/10.1186/s12887-017-0960-3.Search in Google Scholar PubMed PubMed Central

5. Schillaci, L-AP, DeBrosse, SD, McCandless, SE. Inborn errors of metabolism with acidosis. Pediatr Clin North Am 2018;65:209–30. https://doi.org/10.1016/j.pcl.2017.11.003.Search in Google Scholar PubMed

6. Millar, R, Harding, A. Review article: accelerated starvation of childhood: have I judged ketones?. Emerg Med Australas 2019;31:314–20. https://doi.org/10.1111/1742-6723.13276.Search in Google Scholar PubMed

7. Espírito Santo, R, Vaz, S, Jalles, F, Boto, L, Abecasis, F. Salicylate intoxication in an infant: a case report. Drug Saf Case Rep 2017;4:23. https://doi.org/10.1007/s40800-017-0065-9.Search in Google Scholar PubMed PubMed Central

8. Chiang, JL, Maahs, DM, Garvey, KC, Hood, KK, Laffel, LM, Weinzimer, SA, et al. Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care 2018;41:2026–44. https://doi.org/10.2337/dci18-0023.Search in Google Scholar PubMed PubMed Central

9. Wolfsdorf, JI, Glaser, N, Agus, M, Fritsch, M, Hanas, R, Rewers, A, et al. ISPAD clinical practice consensus guidelines 2018: diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes 2018;19:155–77. https://doi.org/10.1111/pedi.12701.Search in Google Scholar PubMed

10. Nguyen, KN, Abdelkreem, E, Colombo, R, Hasegawa, Y, Can, NTB, Bui, TP, et al. Characterization and outcome of 41 patients with beta-ketothiolase deficiency: 10 years’ experience of a medical center in northern Vietnam. J Inherit Metab Dis 2017;40:395–401. https://doi.org/10.1007/s10545-017-0026-6.Search in Google Scholar PubMed

11. Dejkhamron, P, Wejapikul, K, Unachak, K, Sawangareetrakul, P, Tanpaiboon, P, Wattanasirichaigoon, D. Isolated methylmalonic acidemia with unusual presentation mimicking diabetic ketoacidosis. J Pediatr Endocrinol Metab 2016 Jan 1;29:373–8. https://doi.org/10.1515/jpem-2015-0228.Search in Google Scholar PubMed

12. Erdem, E, Cayonu, N, Uysalol, E, Yildirmak, ZY. Chronic intermittent form of isovaleric acidemia mimicking diabetic ketoacidosis. J Pediatr Endocrinol Metab 2010;23:503–5. https://doi.org/10.1515/jpem.2010.082.Search in Google Scholar PubMed

13. Kılıç, M, Kaymaz, N, Özgül, RK. Isovaleric acidemia presenting as diabetic ketoacidosis: a case report. J Clin Res Pediatr Endocrinol 2014;6:59–61. https://doi.org/10.4274/Jcrpe.1181.Search in Google Scholar PubMed PubMed Central

14. Erdol, S, Ture, M, Yakut, T, Saglam, H, Sasai, H, Abdelkreem, E, et al. A Turkish patient with succinyl-CoA:3-oxoacid CoA transferase deficiency mimicking diabetic ketoacidosis. J Inborn Errors Metab Screen 2016;4:1–5. https://doi.org/10.1177/2326409816651281.Search in Google Scholar

15. Benni, JM, Patil, PA. Non-diabetic clinical applications of insulin. J Basic Clin Physiol Pharmacol 2016;27:445–56. https://doi.org/10.1515/jbcpp-2015-0101.Search in Google Scholar PubMed

16. Bideci, A, Yeşilkaya, E. Salicylate intoxication masquerading as diabetic ketoacidosis in a child. Pediatr Int 2008;50:605. https://doi.org/10.1111/j.1442-200x.2008.02699.x.Search in Google Scholar

17. Polak, M, Rolon, MA, Chouchana, A, Czernichow, P. Theophylline intoxication mimicking diabetic ketoacidosis in a child. Diabetes Metab 1999;25:513–5. 10633877.Search in Google Scholar

18. MacFie, C, Wall, E, Ash, S. Paracetamol overdose presenting with hyperglycaemia, acidosis and ketonuria in a non-diabetic patient. Acute Med 2009;8:77–8. 21603675.Search in Google Scholar

19. Le Neveu, F, Hywel, B, Harvey, JN. Euglycaemic ketoacidosis in patients with and without diabetes. Pract Diabetes 2013;30:167–71. https://doi.org/10.1002/pdi.1769.Search in Google Scholar

20. Zhou, W, Luo, L. Preoperative prolonged fasting causes severe metabolic acidosis. Medicine (Baltimore) 2019;98:e17434. https://doi.org/10.1097/md.0000000000017434.Search in Google Scholar

21. Almuqbil, M, Chinsky, JM, Srivastava, S. Metabolic strokes in propionic acidemia: transient hemiplegic events without encephalopathy. Child Neurol Open 2019;6. https://doi.org/10.1177/2329048x19873242.Search in Google Scholar

22. Fukao, T, Sasai, H, Aoyama, Y, Otsuka, H, Ago, Y, Matsumoto, H, et al. Recent advances in understanding beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase, T2) deficiency. J Hum Genet 2019;64:99–111. https://doi.org/10.1038/s10038-018-0524-x.Search in Google Scholar PubMed

23. Ren, S, Chen, Z, Liu, M, Wang, Z. The radiological findings of hypoglycemic encephalopathy: a case report with high B value DWI analysis. Medicine (Baltimore) 2017;96: e8425. https://doi.org/10.1097/md.0000000000008425.Search in Google Scholar PubMed PubMed Central

24. Saudubray, J-M, Garcia-Cazorla, À. Inborn errors of metabolism overview: pathophysiology, manifestations, evaluation, and management. Pediatr Clin North Am 2018;65:179–208. https://doi.org/10.1016/j.pcl.2017.11.002.Search in Google Scholar PubMed

25. Abdelkreem, E, Alobaidy, H, Aoyama, Y, Mahmoud, S, Abd El Aal, M, Fukao, T. Two Libyan siblings with beta-ketothiolase deficiency: a case report and review of literature. Egypt J Med Hum Genet 2017;18:199–203. https://doi.org/10.1016/j.ejmhg.2016.11.001.Search in Google Scholar

26. Abdelkreem, E, Otsuka, H, Sasai, H, Aoyama, Y, Hori, T, Abd El Aal, M, et al. Beta-ketothiolase deficiency: resolving challenges in diagnosis. J Inborn Errors Metab Screen 2016;4:1–9. https://doi.org/10.1177/2326409816636644.Search in Google Scholar

27. Hoogeveen, IJ, van der Ende, RM, van Spronsen, FJ, de Boer, F, Heiner-Fokkema, MR, Derks, TGJ. Normoglycemic ketonemia as biochemical presentation in ketotic glycogen storage disease. JIMD Rep 2015;28:41–7. https://doi.org/10.1007/8904_2015_511.Search in Google Scholar PubMed PubMed Central

28. Sasai, H, Aoyama, Y, Otsuka, H, Abdelkreem, E, Naiki, Y, Kubota, M, et al. Heterozygous carriers of succinyl-CoA: 3-oxoacid CoA transferase deficiency can develop severe ketoacidosis. J Inherit Metab Dis 2017;40:845–52. https://doi.org/10.1007/s10545-017-0065-z.Search in Google Scholar PubMed

29. Ago, Y, Sugie, H, Fukuda, T, Otsuka, H, Sasai, H, Nakama, M, et al. A rare PHKA2 variant (p.G991A) identified in a patient with ketotic hypoglycemia. JIMD Rep 2019;48:15–8. https://doi.org/10.1002/jmd2.12041.Search in Google Scholar PubMed PubMed Central

30. Dahl, GT, Woldseth, B, Lindemann, R. Metabolic acidosis mimicking diabetic ketoacidosis after use of calorie-free mineral water. Eur J Pediatr 2012;171:1405–7. https://doi.org/10.1007/s00431-012-1723-7.Search in Google Scholar PubMed

31. Bonnefont, JP, Specola, NB, Vassault, A, Lombes, A, Ogier, H, de Klerk, JBC, et al. The fasting test in paediatrics: application to the diagnosis of pathological hypo- and hyperketotic states. Eur J Pediatr 1990;150:80–5. https://doi.org/10.1007/bf02072043.Search in Google Scholar PubMed

32. Milroy, CM, Parai, JL. Armanni-Ebstein lesion, ketoacidosis and starvation in a child. Forensic Sci Med Pathol 2011;7:213–6. https://doi.org/10.1007/s12024-010-9213-6.Search in Google Scholar PubMed

33. Dennhardt, N, Beck, C, Huber, D, Nickel, K, Sander, B, Witt, L-H, et al. Impact of preoperative fasting times on blood glucose concentration, ketone bodies and acid–base balance in children younger than 36 months. Eur J Anaesthesiol 2015;32:857–61. https://doi.org/10.1097/eja.0000000000000330.Search in Google Scholar

34. Nakamura, K, Inokuchi, R, Doi, K, Fukuda, T, Tokunaga, K, Nakajima, S, et al. Septic ketoacidosis. Intern Med 2014;53:1071–3. https://doi.org/10.2169/internalmedicine.53.1791.Search in Google Scholar PubMed

35. Chambrier, C, Laville, M, Rhzioual Berrada, K, Odeon, M, Boulétreau, P, Beylot, M. Insulin sensitivity of glucose and fat metabolism in severe sepsis. Clin Sci 2000;99:321–8. https://doi.org/10.1042/cs0990321.Search in Google Scholar

36. Manini, AF, Hoffman, RS, Nelson, LS. Alcoholic ketoacidosis in an 11-year-old boy. Pediatr Emerg Care 2008;24:170–1. https://doi.org/10.1097/pec.0b013e3181669061.Search in Google Scholar PubMed

37. Hassan, FA, El-Mougy, F, Sharaf, SA, Mandour, I, Morgan, MF, Selim, LA, et al. Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: the first newborn screening pilot study. J Med Screen 2016;23:124–9. https://doi.org/10.1177/0969141315618229.Search in Google Scholar PubMed

Received: 2020-06-01
Accepted: 2020-09-03
Published Online: 2020-10-09
Published in Print: 2021-01-27

© 2020 Walter de Gruyter GmbH, Berlin/Boston