---
title: "Fulminant hyperammonemia during chemotherapy linked to occult partial OTC deficiency"
id: "pubmed-42698052"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42698052"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42698052/"
doi: "10.1007/s12185-026-04271-6"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Fulminant hyperammonemia during chemotherapy linked to occult partial OTC deficiency
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42698052
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42698052/)
- **DOI:** [10.1007/s12185-026-04271-6](https://doi.org/10.1007%2Fs12185-026-04271-6)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Reported is a case of a woman in her 40s with **acute myeloid leukemia (AML)** who developed fulminant nonhepatic **hyperammonemia** during high-dose cytarabine consolidation therapy. - On day 5 of consolidation she manifested rapidly progressive altered consciousness with markedly elevated serum ammonia despite preserved liver and kidney function and absence of active sepsis. - Brain MRI demonstrated cortical changes more consistent with **metabolic encephalopathy** than with cytarabine neurotoxicity or posterior reversible encephalopathy syndrome (PRES). - The clinical course progressed to rising ammonia levels, generalized seizures, diffuse cerebral edema, and death despite supportive care. - Metabolic workup suggested a **urea cycle disorder**; genetic testing identified a heterozygous pathogenic variant in the **ornithine transcarbamylase (OTC)** gene, indicating previously unrecognized partial OTC deficiency. - Adult cases of severe nonhepatic hyperammonemia in hematologic malignancy patients are often labeled idiopathic or infection-related; genetically proven urea cycle disorders in this context are rare. - This case broadens the recognized spectrum of chemotherapy-associated nonhepatic hyperammonemia by implicating an occult inherited metabolic predisposition as a potential contributor to pathogenesis. - The report emphasizes the need for early recognition and consideration of hyperammonemia in unexplained encephalopathy during intensive chemotherapy to enable timely metabolic evaluation and management.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # Fulminant hyperammonemia during intensive chemotherapy in the setting of previously unrecognized partial ornithine transcarbamylase deficiency [Risa Hashida](https://pubmed.ncbi.nlm.nih.gov/?term=Hashida+R&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-2 "Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan."), [Ken-Ichi Matsuoka](https://pubmed.ncbi.nlm.nih.gov/?term=Matsuoka+KI&cauthor_id=42698052)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-3 "Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan. k-matsu@tokushima-u.ac.jp."), [Yuki Goto](https://pubmed.ncbi.nlm.nih.gov/?term=Goto+Y&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Kyoichiro Nomura](https://pubmed.ncbi.nlm.nih.gov/?term=Nomura+K&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Yuki Doi](https://pubmed.ncbi.nlm.nih.gov/?term=Doi+Y&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Masaya Abe](https://pubmed.ncbi.nlm.nih.gov/?term=Abe+M&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Ryo Ueda](https://pubmed.ncbi.nlm.nih.gov/?term=Ueda+R&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Kyoko Itakusu](https://pubmed.ncbi.nlm.nih.gov/?term=Itakusu+K&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Kyosuke Saeki](https://pubmed.ncbi.nlm.nih.gov/?term=Saeki+K&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Koichi Nakase](https://pubmed.ncbi.nlm.nih.gov/?term=Nakase+K&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Yuichiro Nawa](https://pubmed.ncbi.nlm.nih.gov/?term=Nawa+Y&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#full-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan.") Affiliations Expand ### Affiliations * 1 Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan. * 2 Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan. * 3 Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan. k-matsu@tokushima-u.ac.jp. * PMID: **42698052** * DOI: [ 10.1007/s12185-026-04271-6 ](https://doi.org/10.1007/s12185-026-04271-6) Item in Clipboard # Fulminant hyperammonemia during intensive chemotherapy in the setting of previously unrecognized partial ornithine transcarbamylase deficiency Risa Hashida et al. Int J Hematol. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Hematol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Hematol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Hematol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42698052/) . 2026 Sep 5. doi: 10.1007/s12185-026-04271-6. Online ahead of print. ### Authors [Risa Hashida](https://pubmed.ncbi.nlm.nih.gov/?term=Hashida+R&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-2 "Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan."), [Ken-Ichi Matsuoka](https://pubmed.ncbi.nlm.nih.gov/?term=Matsuoka+KI&cauthor_id=42698052)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-3 "Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan. k-matsu@tokushima-u.ac.jp."), [Yuki Goto](https://pubmed.ncbi.nlm.nih.gov/?term=Goto+Y&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Kyoichiro Nomura](https://pubmed.ncbi.nlm.nih.gov/?term=Nomura+K&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Yuki Doi](https://pubmed.ncbi.nlm.nih.gov/?term=Doi+Y&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Masaya Abe](https://pubmed.ncbi.nlm.nih.gov/?term=Abe+M&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Ryo Ueda](https://pubmed.ncbi.nlm.nih.gov/?term=Ueda+R&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Kyoko Itakusu](https://pubmed.ncbi.nlm.nih.gov/?term=Itakusu+K&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Kyosuke Saeki](https://pubmed.ncbi.nlm.nih.gov/?term=Saeki+K&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Koichi Nakase](https://pubmed.ncbi.nlm.nih.gov/?term=Nakase+K&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan."), [Yuichiro Nawa](https://pubmed.ncbi.nlm.nih.gov/?term=Nawa+Y&cauthor_id=42698052)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698052/#short-view-affiliation-1 "Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan.") ### Affiliations * 1 Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan. * 2 Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan. * 3 Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan. k-matsu@tokushima-u.ac.jp. * PMID: **42698052** * DOI: [ 10.1007/s12185-026-04271-6 ](https://doi.org/10.1007/s12185-026-04271-6) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Hyperammonemic encephalopathy is a rare but often fatal complication in patients with hematological malignancies receiving intensive therapy, and its underlying mechanism is often unclear. We report the case of a woman in her 40 s with acute myeloid leukemia who developed fulminant nonhepatic hyperammonemia during high-dose cytarabine consolidation in association with previously unrecognized partial ornithine transcarbamylase (OTC) deficiency. On day 5 of consolidation, she developed rapidly progressive altered consciousness with marked hyperammonemia, preserved hepatic and renal function, and no evidence of active sepsis. Brain magnetic resonance imaging showed cortical abnormalities more consistent with metabolic encephalopathy than cytarabine-associated neurotoxicity or posterior reversible encephalopathy syndrome. Despite supportive therapy, serum ammonia increased further, followed by seizures, diffuse cerebral edema, and death. Metabolic evaluation suggested a urea cycle disorder, and genetic testing identified a heterozygous pathogenic OTC variant, indicating an underlying inherited metabolic predisposition. Reported adult cases of severe nonhepatic hyperammonemia in hematological malignancies have largely been considered idiopathic or infection-related, whereas genetically confirmed urea cycle disorders remain rare. This case expands the spectrum of chemotherapy-associated nonhepatic hyperammonemia and suggests that occult inherited metabolic predisposition may contribute to its pathogenesis, highlighting the importance of early recognition of hyperammonemia in unexplained encephalopathy during intensive chemotherapy. **Keywords:** Acute myeloid leukemia; Chemotherapy; Hyperammonemia; Ornithine transcarbamylase deficiency; Urea cycle disorder. © 2026. The Author(s), under exclusive licence to Japanese Society of Hematology. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Conflict of interest: The authors declare there is no conflict of interest. Ethical approval and consent to participate: The study was approved by the institutional review board (approval no. 07–44), and informed consent for publication was obtained from the patient’s family. ## References 1. 1. Metzeler KH, Boeck S, Christ B, Hausmann A, Stemmler HJ, Parhofer KG, 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:e69–72. - [DOI](https://doi.org/10.1016/j.leukres.2009.01.008) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/19230970/) 2. 1. Fayed M, Patel N, Al Turk Y, Bradley PB. Unexplained fatal hyperammonemia in a patient with new diagnosis of acute monoblastic leukemia. Cureus. 2021;13:e20108. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35003956/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8723723/) 3. 1. Davies SM, Szabo E, Wagner JE, Ramsay NKC, Weisdorf DJ. Idiopathic hyperammonemia: a frequently lethal complication of bone marrow transplantation. Bone Marrow Transpl. 1996;17:1119–25. 4. 1. Baker WJ, Royer GL Jr, Weiss RB. Cytarabine and neurologic toxicity. J Clin Oncol. 1991;9:679–93. - [DOI](https://doi.org/10.1200/jco.1991.9.4.679) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/1648599/) 5. 1. Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol. 2008;29:1036–42. - [DOI](https://doi.org/10.3174/ajnr.a0928) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/18356474/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8118828/) Show all 26 references [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM **Send To** * [Clipboard](https://pubmed.ncbi.nlm.nih.gov/42698052/) * [Email](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42698052%2F%23open-email-panel) * [Save](https://pubmed.ncbi.nlm.nih.gov/42698052/) * [My Bibliography](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42698052%2F%23open-bibliography-panel) * [Collections](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42698052%2F%23open-collections-panel) * [Citation Manager](https://pubmed.ncbi.nlm.nih.gov/42698052/) [x] NCBI Literature Resources [MeSH](https://www.ncbi.nlm.nih.gov/mesh/) [PMC](https://www.ncbi.nlm.nih.gov/pmc/) [Bookshelf](https://www.ncbi.nlm.nih.gov/books) [Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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