A critically ill postpartum woman with fatal hyperammonemic encephalopathy by intracranial venous sinus thrombosis

A critically ill postpartum woman with fatal hyperammonemic encephalopathy by intracranial venous sinus thrombosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A critically ill postpartum woman with fatal hyperammonemic encephalopathy by intracranial venous sinus thrombosis Yuehui Zhang, Kaichen Wang, Jun Liu, Nianxia Fu, Zhiwen Chen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6696967/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Key Clinical Message : This case highlights the importance of considering metabolic disorders, such as ornithine transcarbamylase deficiency (OTCD), in postpartum women presenting with altered consciousness, seizures, and neurological deficits. In this 29-year-old patient, the initial diagnosis of transverse sinus thrombosis was complicated by the identification of hyperammonemic encephalopathy, a rare but critical condition. Elevated blood ammonia levels, in conjunction with neuroimaging findings, prompted the diagnosis of OTCD, confirmed by genetic testing. Despite appropriate treatment, the patient experienced irreversible neurological damage, underscoring the need for early recognition and intervention in such cases. ornithine transcarbamylase deficiency (OTCD) transverse sinus thrombosis postpartum hyperammonemic encephalopathy Figures Figure 1 Figure 2 Introduction Acute and severe neurological issues pose a considerable health challenge for pregnant and postpartum patients, occurring at a rate several times higher than in similar nonpregnant groups. Emergency healthcare providers need to be particularly vigilant for disorders of consciousness in these individuals, as prompt diagnosis and urgent treatment can avert serious neurological consequences [ 1 ] . Ornithine transcarbamylase deficiency (OTCD) is a hereditary metabolic disorder and the most common urea cycle disorder (UCD) [ 2 ] . OTCD presents as a spectrum that includes a neonatal acute form, a milder late-onset form, a form in which women have onset of symptoms during pregnancy or postpartum, and a form without symptoms or hyperammonemia [ 3 – 5 ] . Female carriers of genetic defects in metabolic disorders also face the risk of complications during both the intrapartum and postpartum phases. This can potentially cause hyperammonemia, which may result in an acute and critical condition and is prone to misdiagnosis and missed diagnosis. [ 6 , 7 ] In this report, we present a case involving a critically ill postpartum woman with hyperammonemic encephalopathy associated with a genetic defect, complicated by intracranial venous sinus thrombosis. Case presentation A 29-year-old woman in the postpartum period transferred to the intensive care medicine department with a 5-day history of diminished responsiveness and 1 day of seizures accompanied by altered consciousness. She has a history of adverse obstetric outcomes, including a deceased male newborn and a female child with congenital disabilities. The patient was admitted in a deep sedated state, and liver function indicators such as transaminases, bilirubin, albumin, and bile acid metabolism remained within normal limits. A pre-admission brain CT angiography suggested thrombosis of the left transverse sinus (Fig. 1, A-C). During the subsequent 18 days of treatment, we maintained anticoagulation. When sedation and analgesia were reduced, seizures occurred that were not consistent with the progression of transverse sinus thrombosis. A follow-up diffusion-weighted image (DWI) showed reduced diffusion in the cerebral cortex, especially in the cingulate gyrus and insular cortex (Fig. 1D) and fluid-attenuated inversion recovery (FLAIR) sequence also revealed extensive symmetric and bilateral cortical parenchymal abnormality (Fig. 1E), which suggesting hyperammonemic encephalopathy. MRV showed filling defects in the left transverse sinus. We promptly checked the blood ammonia level, which was alarmingly high at 395 µmol/L (reference range: 9–30). Upon discussing the medical history with the family, we discovered a supplementary report from whole-genome sequencing (family study) indicating that the patient had heterozygous mutation in the OTC gene (c.421C > T; p.Arg141*) associated with ornithine transcarbamylase deficiency (OTCD) (Fig. 2). Despite treatment, which included strategies for brain protection and continuous venovenous hemofiltration (CVVH) to reduce blood ammonia levels, the patient's brain function had already sustained irreversible damage. Discussion The distinct pathophysiological changes occurring during the early puerperium elevate the risk of thromboembolism and hypertension. These alterations may exacerbate preexisting neurological conditions, or patients may present with new, acute-onset neurological disorders [ 8 – 10 ] . Ornithine transcarbamylase deficiency (OTCD) is an X-linked genetic disorder that interferes with the urea cycle, thereby compromising the body's ability to metabolize ammonia. The urea cycle represents the sole metabolic pathway for the irreversible removal of excess nitrogen via ureagenesis in humans. Disruption of this pathway results in the accumulation of ammonia and glutamine in the plasma. As a result, individuals affected by this condition frequently exhibit severe, life-threatening hyperammonemic events (HAE) [ 11 ] .Consequently, we hypothesize that the patient's hyperammonemic encephalopathy is attributable to this genetic mutation. In male individuals, the condition frequently presents as a severe hyperammonemic crisis during the neonatal period, which can lead to neonatal mortality. Heterozygous women may be asymptomatic or have varying degrees of clinical manifestation. The family shows this trait as well, and we speculate that the deceased male newborns among the patient’s children also carried this genetic defect. Additionally, female carriers are at risk of pregnancy complications too, as both the intrapartum and postpartum periods are catabolic states, possibly triggering hyperammonemia, potentially leading to life-threatening encephalopathy. The interval from the third to the fourteenth day postpartum is regarded as particularly critical for the occurrence of metabolic decompensations [ 6 , 7 ] . It is suggested that the removal of the nitrogen-absorbing fetal-placental unit, along with the shrinking of the uterus that releases surplus nitrogen, leads to elevated nitrogen levels, which in turn may cause hyperammonemia [ 12 – 14 ] . During this timeframe, this patient's condition deteriorated. Regrettably, the absence of a thorough genetic history collection resulted in the missed opportunity for perinatal intervention and timely treatment was missed. Furthermore, literature reports suggest that individuals with OTCD may have a higher likelihood of developing thrombosis [ 7 ] . In addition to the hypercoagulability during pregnancy and puerperium [ 15 ] may explain the occurrence of transverse sinus thrombosis in this patient. The clinical presentation and severity of OTCD can vary widely. Some female carriers may not show symptoms until they are pregnant or in the postpartum period. OTCD should be suspected in cases of adverse pregnancy outcomes, unexplained coma in women, signs of cerebral edema, respiratory alkalosis with hyperventilation, recurrent vomiting, lethargy, unusual behavior, ataxia, and a history of selective anorexia, particularly regarding high-protein foods [ 16 , 17 ] . Physicians should conduct a comprehensive medical history and thorough evaluation, which includes checking ammonia levels to identify hyperammonemia, as well as reviewing other relevant laboratory tests and performing Magnetic Resonance Imaging (MRI) to exclude other potential diagnoses [ 12 ] . In the event of an acute episode of hyperammonemia during labor, it is essential to halt protein intake and provide nutrition through 10% dextrose to prevent further protein breakdown and ammonia buildup. An additional infusion of intralipid therapy can offer extra calories. If the plasma ammonia level nears three times the normal range, arginine, sodium benzoate, and sodium phenylbutyrate should be given [ 16 ] . If ammonia levels do not decrease within 8 hours of treatment, or if there is a sudden increase to 250 mg/dL, hemodialysis should be initiated [ 18 ] . This case suggests that critical pregnant women may have particularly complex conditions under various pathophysiological mechanisms. It is important to pay attention to the implications of adverse pregnancy history in perinatal patients regarding hereditary diseases and to ensure proper management of perinatal pregnant women and the treatment of critically ill pregnant patients. Conclusion This case highlights the role of genetic, metabolic, and physiological factors in postpartum women, particularly those with adverse pregnancy outcomes. Ornithine transcarbamylase deficiency (OTCD) can cause life-threatening hyperammonemic encephalopathy during the catabolic postpartum period. The patient`s symptoms emphasize the need to consider OTCD in unexplained neurological cases. Timely genetic screening and hyperammonemia management are crucial to prevent irreversible damage, underscoring the need for comprehensive treatment in critically ill pregnant women. Declarations Funding information Study funding was provided by 2024 High-quality Development Research Project of Shenzhen Bao'an Public Hospital (BAGZL2024045) and Health and Medical Scientific Research Project of Shenzhen Bao'an Medical Association (BAYXH2023024). No other disclosures were reported. Ethics statement No ethical approval is needed in our institute for case reports. Consent Written informed consent was obtained from the patient to publish this report by the journal's patient consent policy. Author contributions: Yuehui Zhang: Writing – original draft, Writing – review, editing, Funding acquisition. Kaichen Wang: Resources, investigation. Jun Liu: Visualization. Supervision. Nianxia Fu : investigation. Zhiwen Chen: Visualization. Yingte Wu: Supervision. Shengyuan Su : Writing—review and editing. Declaration of competing interest The authors declare there are no potential/perceived conflicts of interest. Acknowledgments We thank the parents and husband of the patients for granting permission to publish this information. References Steinberg AE, practice VSJEm. Emergency department management of stroke in pregnant and postpartum patients. 2023;25(Suppl 12):1-37. https://www.ncbi.nlm.nih.gov/pubmed/38085603. Donovan K, Vaqar S, Guzman N. Ornithine Transcarbamylase Deficiency. StatPearls , Treasure Island (FL) ineligible companies. Disclosure: Sarosh Vaqar declares no relevant financial relationships with ineligible companies. Disclosure: Nilmarie Guzman declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2025, StatPearls Publishing LLC.; 2025. Ibrahim MS, Gold JI, Woodall A, Yilmaz BS, Gissen P, Children KMSJ. Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency. 2023;10(8)https://doi.org/10.3390/children10081368. Sen K, Izem R, Long Y, Jiang J, Konczal LL, McCarter RJ, et al. Are asymptomatic carriers of OTC deficiency always asymptomatic? A multicentric retrospective study of risk using the UCDC longitudinal study database. 2024;12(4):e2443. https://doi.org/10.1002/mgg3.2443. Torkzaban M, Haddad A, Baxter JK, Berghella V, Gahl WA, A HBA-KJAjomgP. Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: A systematic review. 2019;179(10):2091-100. https://doi.org/10.1002/ajmg.a.61329. Sysák R, Brennerová K, Krlín R, Štencl P, Rusňák I, Diagnostics MVJ. Effect of Ornithine Transcarbamylase (OTC) Deficiency on Pregnancy and Puerperium. 2022;12(2)https://doi.org/10.3390/diagnostics12020415. Venkateswaran L, Scaglia F, McLin V, Hertel P, Shchelochkov OA, Karpen S, et al. Ornithine transcarbamylase deficiency: a possible risk factor for thrombosis. 2009;53(1):100-2. https://doi.org/10.1002/pbc.22016. Sidorov EV, Feng W, therapy LRCJEroc. Stroke in pregnant and postpartum women. 2011;9(9):1235-47. https://doi.org/10.1586/erc.11.98. Cipolla MJ, Bishop N, Hypertension S-LCJ. Effect of pregnancy on autoregulation of cerebral blood flow in anterior versus posterior cerebrum. 2012;60(3):705-11. https://doi.org/10.1161/hypertensionaha.112.198952. Edlow AG, Edlow BL, America JAEJEmcoN. Diagnosis of Acute Neurologic Emergencies in Pregnant and Postpartum Women. 2016;34(4):943-65. https://doi.org/10.1016/j.emc.2016.06.014. Scharre S, Posset R, Garbade SF, Gleich F, Seidl MJ, Druck A-C, et al. Predicting the disease severity in male individuals with ornithine transcarbamylase deficiency. 2022;9(11):1715-26. https://doi.org/10.1002/acn3.51668. Pinho G, Ross G, Krishnamoorthy K, Kresge C, Shih LY, Apuzzio JJ, et al. Ornithine transcarbamylase deficiency and pregnancy: A case series and review of recommendations. 2022;34:e00390. https://doi.org/10.1016/j.crwh.2022.e00390. Lamb S, Aye CYL, Murphy E, reports LMJBc. Multidisciplinary management of ornithine transcarbamylase (OTC) deficiency in pregnancy: essential to prevent hyperammonemic complications. 2013;2013https://doi.org/10.1136/bcr-2012-007416. Celik O, Buyuktas D, Aydin A, Endocrinology OAJGetojotISoG. Ornithine transcarbamylase deficiency diagnosed in pregnancy. 2011;27(12):1052-4. https://doi.org/10.3109/09513590.2011.569787. Silvis SM, Lindgren E, Hiltunen S, Devasagayam S, Scheres LJ, Jood K, et al. Postpartum Period Is a Risk Factor for Cerebral Venous Thrombosis. 2019;50(2):501-3. https://doi.org/10.1161/strokeaha.118.023017. Ituk U, Constantinescu OC, Allen TK, Small MJ, anesthesia ASHJIjoo. Peripartum management of two parturients with ornithine transcarbamylase deficiency. 2012;21(1):90-3. https://doi.org/10.1016/j.ijoa.2011.09.007. Lichter-Konecki U, Caldovic L, Morizono H, Simpson K, Ah Mew N, MacLeod E. Ornithine Transcarbamylase Deficiency. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) , Seattle (WA): University of Washington, Seattle Copyright © 1993-2025, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993. Mendez-Figueroa H, Lamance K, Sutton VR, Aagaard-Tillery K, perinatology IVdVJAjo. Management of ornithine transcarbamylase deficiency in pregnancy. 2010;27(10):775-84. https://doi.org/10.1055/s-0030-1254240. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6696967","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":494321561,"identity":"e7067f96-c516-4e69-be02-da0cbbcdbef7","order_by":0,"name":"Yuehui Zhang","email":"","orcid":"","institution":"The Second Affiliated Hospital of Shenzhen University","correspondingAuthor":false,"prefix":"","firstName":"Yuehui","middleName":"","lastName":"Zhang","suffix":""},{"id":494321562,"identity":"c94f3325-212e-4502-b687-4efd114b3d78","order_by":1,"name":"Kaichen Wang","email":"","orcid":"","institution":"The Second Affiliated Hospital of Shenzhen 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11:11:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":203455,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6696967/v1/bdcce49e4c92f22a3b37a6d4.png"},{"id":88241162,"identity":"f7dcb37a-b0f5-401e-9b75-d9a0a3a5b22a","added_by":"auto","created_at":"2025-08-04 11:19:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":999243,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6696967/v1/bd88753c-e498-4b64-93ee-43c216ce5b79.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eA critically ill postpartum woman with fatal hyperammonemic encephalopathy by intracranial venous sinus thrombosis\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute and severe neurological issues pose a considerable health challenge for pregnant and postpartum patients, occurring at a rate several times higher than in similar nonpregnant groups. Emergency healthcare providers need to be particularly vigilant for disorders of consciousness in these individuals, as prompt diagnosis and urgent treatment can avert serious neurological consequences\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOrnithine transcarbamylase deficiency (OTCD) is a hereditary metabolic disorder and the most common urea cycle disorder (UCD)\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. OTCD presents as a spectrum that includes a neonatal acute form, a milder late-onset form, a form in which women have onset of symptoms during pregnancy or postpartum, and a form without symptoms or hyperammonemia\u003csup\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e–\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Female carriers of genetic defects in metabolic disorders also face the risk of complications during both the intrapartum and postpartum phases. This can potentially cause hyperammonemia, which may result in an acute and critical condition and is prone to misdiagnosis and missed diagnosis.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn this report, we present a case involving a critically ill postpartum woman with hyperammonemic encephalopathy associated with a genetic defect, complicated by intracranial venous sinus thrombosis.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 29-year-old woman in the postpartum period transferred to the intensive care medicine department with a 5-day history of diminished responsiveness and 1 day of seizures accompanied by altered consciousness. She has a history of adverse obstetric outcomes, including a deceased male newborn and a female child with congenital disabilities. The patient was admitted in a deep sedated state, and liver function indicators such as transaminases, bilirubin, albumin, and bile acid metabolism remained within normal limits. A pre-admission brain CT angiography suggested thrombosis of the left transverse sinus (Fig.\u0026nbsp;1, A-C). During the subsequent 18 days of treatment, we maintained anticoagulation. When sedation and analgesia were reduced, seizures occurred that were not consistent with the progression of transverse sinus thrombosis. A follow-up diffusion-weighted image (DWI) showed reduced diffusion in the cerebral cortex, especially in the cingulate gyrus and insular cortex (Fig.\u0026nbsp;1D) and fluid-attenuated inversion recovery (FLAIR) sequence also revealed extensive symmetric and bilateral cortical parenchymal abnormality (Fig.\u0026nbsp;1E), which suggesting hyperammonemic encephalopathy. MRV showed filling defects in the left transverse sinus. We promptly checked the blood ammonia level, which was alarmingly high at 395 µmol/L (reference range: 9–30). Upon discussing the medical history with the family, we discovered a supplementary report from whole-genome sequencing (family study) indicating that the patient had heterozygous mutation in the OTC gene (c.421C \u0026gt; T; p.Arg141*) associated with ornithine transcarbamylase deficiency (OTCD) (Fig.\u0026nbsp;2). Despite treatment, which included strategies for brain protection and continuous venovenous hemofiltration (CVVH) to reduce blood ammonia levels, the patient's brain function had already sustained irreversible damage.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe distinct pathophysiological changes occurring during the early puerperium elevate the risk of thromboembolism and hypertension. These alterations may exacerbate preexisting neurological conditions, or patients may present with new, acute-onset neurological disorders\u003csup\u003e[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOrnithine transcarbamylase deficiency (OTCD) is an X-linked genetic disorder that interferes with the urea cycle, thereby compromising the body's ability to metabolize ammonia. The urea cycle represents the sole metabolic pathway for the irreversible removal of excess nitrogen via ureagenesis in humans. Disruption of this pathway results in the accumulation of ammonia and glutamine in the plasma. As a result, individuals affected by this condition frequently exhibit severe, life-threatening hyperammonemic events (HAE)\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.Consequently, we hypothesize that the patient's hyperammonemic encephalopathy is attributable to this genetic mutation. In male individuals, the condition frequently presents as a severe hyperammonemic crisis during the neonatal period, which can lead to neonatal mortality. Heterozygous women may be asymptomatic or have varying degrees of clinical manifestation. The family shows this trait as well, and we speculate that the deceased male newborns among the patient\u0026rsquo;s children also carried this genetic defect.\u003c/p\u003e\u003cp\u003eAdditionally, female carriers are at risk of pregnancy complications too, as both the intrapartum and postpartum periods are catabolic states, possibly triggering hyperammonemia, potentially leading to life-threatening encephalopathy. The interval from the third to the fourteenth day postpartum is regarded as particularly critical for the occurrence of metabolic decompensations\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. It is suggested that the removal of the nitrogen-absorbing fetal-placental unit, along with the shrinking of the uterus that releases surplus nitrogen, leads to elevated nitrogen levels, which in turn may cause hyperammonemia\u003csup\u003e[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. During this timeframe, this patient's condition deteriorated. Regrettably, the absence of a thorough genetic history collection resulted in the missed opportunity for perinatal intervention and timely treatment was missed.\u003c/p\u003e\u003cp\u003eFurthermore, literature reports suggest that individuals with OTCD may have a higher likelihood of developing thrombosis\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. In addition to the hypercoagulability during pregnancy and puerperium\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e may explain the occurrence of transverse sinus thrombosis in this patient.\u003c/p\u003e\u003cp\u003eThe clinical presentation and severity of OTCD can vary widely. Some female carriers may not show symptoms until they are pregnant or in the postpartum period. OTCD should be suspected in cases of adverse pregnancy outcomes, unexplained coma in women, signs of cerebral edema, respiratory alkalosis with hyperventilation, recurrent vomiting, lethargy, unusual behavior, ataxia, and a history of selective anorexia, particularly regarding high-protein foods\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. Physicians should conduct a comprehensive medical history and thorough evaluation, which includes checking ammonia levels to identify hyperammonemia, as well as reviewing other relevant laboratory tests and performing Magnetic Resonance Imaging (MRI) to exclude other potential diagnoses\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn the event of an acute episode of hyperammonemia during labor, it is essential to halt protein intake and provide nutrition through 10% dextrose to prevent further protein breakdown and ammonia buildup. An additional infusion of intralipid therapy can offer extra calories. If the plasma ammonia level nears three times the normal range, arginine, sodium benzoate, and sodium phenylbutyrate should be given\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. If ammonia levels do not decrease within 8 hours of treatment, or if there is a sudden increase to 250 mg/dL, hemodialysis should be initiated\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThis case suggests that critical pregnant women may have particularly complex conditions under various pathophysiological mechanisms. It is important to pay attention to the implications of adverse pregnancy history in perinatal patients regarding hereditary diseases and to ensure proper management of perinatal pregnant women and the treatment of critically ill pregnant patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights the role of genetic, metabolic, and physiological factors in postpartum women, particularly those with adverse pregnancy outcomes. Ornithine transcarbamylase deficiency (OTCD) can cause life-threatening hyperammonemic encephalopathy during the catabolic postpartum period. The patient`s symptoms emphasize the need to consider OTCD in unexplained neurological cases. Timely genetic screening and hyperammonemia management are crucial to prevent irreversible damage, underscoring the need for comprehensive treatment in critically ill pregnant women.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy funding was provided by 2024 High-quality Development Research Project of Shenzhen Bao'an Public Hospital (BAGZL2024045) and Health and Medical Scientific Research Project of Shenzhen Bao'an Medical Association (BAYXH2023024). No other disclosures were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo ethical approval is needed in our institute for case reports.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient to publish this report by the journal's patient consent policy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYuehui Zhang:\u0026nbsp;\u003c/strong\u003eWriting – original draft, Writing – review, editing, Funding acquisition. \u003cstrong\u003eKaichen Wang:\u0026nbsp;\u003c/strong\u003eResources, investigation. \u003cstrong\u003eJun Liu:\u003c/strong\u003e Visualization. Supervision.\u003cstrong\u003e\u0026nbsp;Nianxia Fu\u003c/strong\u003e: investigation.\u003cstrong\u003e\u0026nbsp;Zhiwen Chen:\u0026nbsp;\u003c/strong\u003eVisualization. \u003cstrong\u003eYingte Wu:\u0026nbsp;\u003c/strong\u003eSupervision. \u003cstrong\u003eShengyuan Su\u003c/strong\u003e: Writing—review and editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of competing interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare there are no potential/perceived conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the parents and husband of the patients for granting permission to publish this information.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSteinberg AE, practice VSJEm. Emergency department management of stroke in pregnant and postpartum patients. 2023;25(Suppl 12):1-37. https://www.ncbi.nlm.nih.gov/pubmed/38085603.\u003c/li\u003e\n\u003cli\u003eDonovan K, Vaqar S, Guzman N. Ornithine Transcarbamylase Deficiency. StatPearls\u003cem\u003e,\u003c/em\u003e Treasure Island (FL) ineligible companies. Disclosure: Sarosh Vaqar declares no relevant financial relationships with ineligible companies. Disclosure: Nilmarie Guzman declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright \u0026copy; 2025, StatPearls Publishing LLC.; 2025.\u003c/li\u003e\n\u003cli\u003eIbrahim MS, Gold JI, Woodall A, Yilmaz BS, Gissen P, Children KMSJ. Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency. 2023;10(8)https://doi.org/10.3390/children10081368.\u003c/li\u003e\n\u003cli\u003eSen K, Izem R, Long Y, Jiang J, Konczal LL, McCarter RJ, et al. Are asymptomatic carriers of OTC deficiency always asymptomatic? A multicentric retrospective study of risk using the UCDC longitudinal study database. 2024;12(4):e2443. https://doi.org/10.1002/mgg3.2443.\u003c/li\u003e\n\u003cli\u003eTorkzaban M, Haddad A, Baxter JK, Berghella V, Gahl WA, A HBA-KJAjomgP. Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: A systematic review. 2019;179(10):2091-100. https://doi.org/10.1002/ajmg.a.61329.\u003c/li\u003e\n\u003cli\u003eSys\u0026aacute;k R, Brennerov\u0026aacute; K, Krl\u0026iacute;n R, \u0026Scaron;tencl P, Rusň\u0026aacute;k I, Diagnostics MVJ. Effect of Ornithine Transcarbamylase (OTC) Deficiency on Pregnancy and Puerperium. 2022;12(2)https://doi.org/10.3390/diagnostics12020415.\u003c/li\u003e\n\u003cli\u003eVenkateswaran L, Scaglia F, McLin V, Hertel P, Shchelochkov OA, Karpen S, et al. Ornithine transcarbamylase deficiency: a possible risk factor for thrombosis. 2009;53(1):100-2. https://doi.org/10.1002/pbc.22016.\u003c/li\u003e\n\u003cli\u003eSidorov EV, Feng W, therapy LRCJEroc. Stroke in pregnant and postpartum women. 2011;9(9):1235-47. https://doi.org/10.1586/erc.11.98.\u003c/li\u003e\n\u003cli\u003eCipolla MJ, Bishop N, Hypertension S-LCJ. Effect of pregnancy on autoregulation of cerebral blood flow in anterior versus posterior cerebrum. 2012;60(3):705-11. https://doi.org/10.1161/hypertensionaha.112.198952.\u003c/li\u003e\n\u003cli\u003eEdlow AG, Edlow BL, America JAEJEmcoN. Diagnosis of Acute Neurologic Emergencies in Pregnant and Postpartum Women. 2016;34(4):943-65. https://doi.org/10.1016/j.emc.2016.06.014.\u003c/li\u003e\n\u003cli\u003eScharre S, Posset R, Garbade SF, Gleich F, Seidl MJ, Druck A-C, et al. Predicting the disease severity in male individuals with ornithine transcarbamylase deficiency. 2022;9(11):1715-26. https://doi.org/10.1002/acn3.51668.\u003c/li\u003e\n\u003cli\u003ePinho G, Ross G, Krishnamoorthy K, Kresge C, Shih LY, Apuzzio JJ, et al. Ornithine transcarbamylase deficiency and pregnancy: A case series and review of recommendations. 2022;34:e00390. https://doi.org/10.1016/j.crwh.2022.e00390.\u003c/li\u003e\n\u003cli\u003eLamb S, Aye CYL, Murphy E, reports LMJBc. Multidisciplinary management of ornithine transcarbamylase (OTC) deficiency in pregnancy: essential to prevent hyperammonemic complications. 2013;2013https://doi.org/10.1136/bcr-2012-007416.\u003c/li\u003e\n\u003cli\u003eCelik O, Buyuktas D, Aydin A, Endocrinology OAJGetojotISoG. Ornithine transcarbamylase deficiency diagnosed in pregnancy. 2011;27(12):1052-4. https://doi.org/10.3109/09513590.2011.569787.\u003c/li\u003e\n\u003cli\u003eSilvis SM, Lindgren E, Hiltunen S, Devasagayam S, Scheres LJ, Jood K, et al. Postpartum Period Is a Risk Factor for Cerebral Venous Thrombosis. 2019;50(2):501-3. https://doi.org/10.1161/strokeaha.118.023017.\u003c/li\u003e\n\u003cli\u003eItuk U, Constantinescu OC, Allen TK, Small MJ, anesthesia ASHJIjoo. Peripartum management of two parturients with ornithine transcarbamylase deficiency. 2012;21(1):90-3. https://doi.org/10.1016/j.ijoa.2011.09.007.\u003c/li\u003e\n\u003cli\u003eLichter-Konecki U, Caldovic L, Morizono H, Simpson K, Ah Mew N, MacLeod E. Ornithine Transcarbamylase Deficiency. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(\u0026reg;)\u003cem\u003e,\u003c/em\u003e Seattle (WA): University of Washington, Seattle Copyright \u0026copy; 1993-2025, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.\u003c/li\u003e\n\u003cli\u003eMendez-Figueroa H, Lamance K, Sutton VR, Aagaard-Tillery K, perinatology IVdVJAjo. Management of ornithine transcarbamylase deficiency in pregnancy. 2010;27(10):775-84. https://doi.org/10.1055/s-0030-1254240.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ornithine transcarbamylase deficiency (OTCD), transverse sinus thrombosis, postpartum, hyperammonemic encephalopathy","lastPublishedDoi":"10.21203/rs.3.rs-6696967/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6696967/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eKey Clinical Message\u003c/b\u003e: This case highlights the importance of considering metabolic disorders, such as ornithine transcarbamylase deficiency (OTCD), in postpartum women presenting with altered consciousness, seizures, and neurological deficits. In this 29-year-old patient, the initial diagnosis of transverse sinus thrombosis was complicated by the identification of hyperammonemic encephalopathy, a rare but critical condition. Elevated blood ammonia levels, in conjunction with neuroimaging findings, prompted the diagnosis of OTCD, confirmed by genetic testing. Despite appropriate treatment, the patient experienced irreversible neurological damage, underscoring the need for early recognition and intervention in such cases.\u003c/p\u003e","manuscriptTitle":"A critically ill postpartum woman with fatal hyperammonemic encephalopathy by intracranial venous sinus thrombosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-04 11:11:21","doi":"10.21203/rs.3.rs-6696967/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-08-10T14:21:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"215161694592631783512307935863676977188","date":"2025-08-01T12:59:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-31T17:38:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310937670022923102693891665093950001310","date":"2025-07-30T16:58:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-30T12:57:21+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-03T09:19:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-27T07:48:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-27T07:45:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-05-19T08:50:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9a2ffbef-8c95-4797-9cf6-0b6f09fe0602","owner":[],"postedDate":"August 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-08-04T11:11:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-04 11:11:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6696967","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6696967","identity":"rs-6696967","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}