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CC BY 4.0 · Journal of Child Science 2021; 11(01): e208-e211
DOI: 10.1055/s-0041-1733871
Case Report

Transient Hyperammonemic Encephalopathy in a Child with Relapsed Acute Lymphoblastic Leukemia and Severe Tumor Lysis Syndrome

Ilja Dubinski 
1   Department for Pediatric Critical Care Medicine, Ludwig Maximilians University Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Tobias Feuchtinger
2   Department for Pediatric Oncology, Hematology and Hemostaseology and Stem Cell Transplantation, Ludwig Maximilians University Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Esther Maier
3   Department for Inborn Errors of Metabolism, Ludwig Maximilians University Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Moritz Tacke
4   Department for Pediatric Neurology, Ludwig Maximilians University Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Florian Hoffmann
1   Department for Pediatric Critical Care Medicine, Ludwig Maximilians University Munich, Dr. von Hauner Children's Hospital, Munich, Germany
› Author Affiliations Funding None.
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Abstract

Idiopathic hyperammonemia (IHA) is a severe condition, which has been reported in intensive chemotherapy and bone marrow transplantation. This case elucidates the diagnostic dilemma in children undergoing initiation of chemotherapy and developing severe disorders of qualitative and quantitative consciousness in the presence of hyperammonemia (HA) and lactic acidosis. The role of mitoxantrone as a causative agent for IHA in children is elusive. Children undergoing chemotherapy are often in a poor general condition, and the clinical presentation of HA is heterogeneous. This case should be a reminder for clinicians to check for HA in children with tumor lysis syndrome and acute neurological deterioration.

Keywords

hyperammonemia - hyperammonemic encephalopathy - common acute lymphoblastic leukemia


Publication History

Received: 11 February 2021

Accepted: 14 June 2021

Article published online:
31 July 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
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  • References

  • 1 Auron A, Brophy PD. Hyperammonemia in review: pathophysiology, diagnosis, and treatment. Pediatr Nephrol 2012; 27 (02) 207-222
    CrossrefPubMedGoogle Scholar
  • 2 Davies SM, Szabo E, Wagner JE, Ramsay NK, Weisdorf DJ. Idiopathic hyperammonemia: a frequently lethal complication of bone marrow transplantation. Bone Marrow Transplant 1996; 17 (06) 1119-1125
    PubMedGoogle Scholar
  • 3 Leonard JV, Kay JD. Acute encephalopathy and hyperammonaemia complicating treatment of acute lymphoblastic leukaemia with asparaginase. Lancet 1986; 1 (8473): 162-163
    CrossrefPubMedGoogle Scholar
  • 4 Nott L, Price TJ, Pittman K, Patterson K, Fletcher J. Hyperammonemia encephalopathy: an important cause of neurological deterioration following chemotherapy. Leuk Lymphoma 2007; 48 (09) 1702-1711
    CrossrefPubMedGoogle Scholar
  • 5 Mitchell RB, Wagner JE, Karp JE. et al. Syndrome of idiopathic hyperammonemia after high-dose chemotherapy: review of nine cases. Am J Med 1988; 85 (05) 662-667
    CrossrefPubMedGoogle Scholar
  • 6 Jaing T-H, Lin J-L, Lin Y-P, Yang S-H, Lin J-J, Hsia S-H. Hyperammonemic encephalopathy after induction chemotherapy for acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2009; 31 (12) 955-956
    CrossrefPubMedGoogle Scholar
  • 7 Watson AJ, Chambers T, Karp JE, Risch VR, Walker WG, Brusilow SW. Transient idiopathic hyperammonemia in adults. Lancet 1985; 2 (8467): 1271-1274
    CrossrefPubMedGoogle Scholar
  • 8 Espinós J, Rifón J, Pérez-Calvo J, Nieto Y. Idiopathic hyperammonemia following high-dose chemotherapy. Bone Marrow Transplant 2006; 37 (09) 899-899
    CrossrefPubMedGoogle Scholar
  • 9 Ho AY, Mijovic A, Pagliuca A, Mufti GJ. Idiopathic hyperammonemia syndrome following allogeneic peripheral blood progenitor cell transplantation (allo-PBPCT). Bone Marrow Transplant 1997; 20 (11) 1007-1008
    CrossrefPubMedGoogle Scholar
  • 10 Tse N, Cederbaum S, Glaspy JA. Hyperammonemia following allogeneic bone marrow transplantation. Am J Hematol 1991; 38 (02) 140-141
    CrossrefPubMedGoogle Scholar
  • 11 Thomas SA, Tomeh N, Theard S. Fluorouracil-induced hyperammonemia in a patient with colorectal cancer. Anticancer Res 2015; 35 (12) 6761-6763
    PubMedGoogle Scholar
  • 12 Snyder MJ, Bradford WD, Kishnani PS, Hale LP. Idiopathic hyperammonemia following an unrelated cord blood transplant for mucopolysaccharidosis I. Pediatr Dev Pathol 2003; 6 (01) 78-83
    CrossrefPubMedGoogle Scholar
  • 13 Lichtenstein GR, Yang Y-X, Nunes FA. et al. Fatal hyperammonemia after orthotopic lung transplantation. Ann Intern Med 2000; 132 (04) 283-287
    CrossrefPubMedGoogle Scholar
  • 14 Kobayashi S, Ito M, Sano H. et al. Idiopathic hyperammonemia that developed during initial treatment with steroid in a patient with newly diagnosed leukemia. J Pediatr Hematol Oncol 2015; 37 (06) e361-e363
    CrossrefPubMedGoogle Scholar
  • 15 Metzeler KH, Boeck S, Christ B. et al. Idiopathic hyperammonemia (IHA) after dose-dense induction chemotherapy for acute myeloid leukemia: case report and review of the literature. Leuk Res 2009; 33 (07) e69-e72
    CrossrefPubMedGoogle Scholar
  • 16 Rossato LG, Costa VM, Dallegrave E. et al. Mitochondrial cumulative damage induced by mitoxantrone: late onset cardiac energetic impairment. Cardiovasc Toxicol 2014; 14 (01) 30-40
    CrossrefPubMedGoogle Scholar
  • 17 Nickel RS, Keller F, Bergsagel J. et al. Mitoxantrone as a substitute for daunorubicin during induction in newly diagnosed lymphoblastic leukemia and lymphoma. Pediatr Blood Cancer 2014; 61 (05) 810-814
    CrossrefPubMedGoogle Scholar
  • 18 del Rosario M, Werlin SL, Lauer SJ. Hyperammonemic encephalopathy after chemotherapy. Survival after treatment with sodium benzoate and sodium phenylacetate. J Clin Gastroenterol 1997; 25 (04) 682-684
    CrossrefPubMedGoogle Scholar
  • 19 Jörck C, Kiess W, Weigel JFW, Mütze U, Bierbach U, Beblo S. Transient hyperammonemia due to L-asparaginase therapy in children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Pediatr Hematol Oncol 2011; 28 (01) 3-9
    CrossrefPubMedGoogle Scholar
  • 20 Heitink-Pollé KMJ, Prinsen BHCMT, de Koning TJ, van Hasselt PM, Bierings MB. High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase. In: Brown G, Morava E, Peters V, Gibson KM, Zschocke J. eds. JIMD Reports: Case and Research Reports, 2012/4. Vol 7. JIMD Reports. Springer Berlin Heidelberg; 2012: 103-108
    Google Scholar
  • 21 Steiner M, Attarbaschi A, Kastner U. et al. Distinct fluctuations of ammonia levels during asparaginase therapy for childhood acute leukemia. Pediatr Blood Cancer 2007; 49 (05) 640-642
    CrossrefPubMedGoogle Scholar
  • 22 Stock W, Douer D, DeAngelo DJ. et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma 2011; 52 (12) 2237-2253
    CrossrefPubMedGoogle Scholar
  • 23 Peters M, Zee-Cheng J, Kuhl A, Orozco J, Lally E, Schwoerer JS. Pegylated asparaginase as cause of fatal hyperammonemia in patients with latent urea cycle disorder. Pediatr Blood Cancer 2018; 65 (09) e27239
    CrossrefPubMedGoogle Scholar
  • 24 Czogała M, Balwierz W, Sztefko K, Rogatko I. Clinical utility of ammonia concentration as a diagnostic test in monitoring of the treatment with L-asparaginase in children with acute lymphoblastic leukemia. BioMed Res Int 2014; 2014: 945860
    CrossrefPubMedGoogle Scholar
  • 25 Koenig H, Patel A. Biochemical basis for fluorouracil neurotoxicity. The role of Krebs cycle inhibition by fluoroacetate. Arch Neurol 1970; 23 (02) 155-160
    CrossrefPubMedGoogle Scholar
  • 26 Cohn RM, Roth KS. Hyperammonemia, bane of the brain. Clin Pediatr (Phila) 2004; 43 (08) 683-689
    CrossrefPubMedGoogle Scholar
  • 27 Kohn MC, Tohmaz AS, Giroux KJ, Blumenthal GM, Feezor MD, Millington DS. Robustness of MetaNet graph models: predicting control of urea production in humans. Biosystems 2002; 65 (01) 61-78
    CrossrefPubMedGoogle Scholar