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Paracetamol toxicity in classic homocystinuria: Effect of N -acetylcysteine on total homocysteine.

التفاصيل البيبلوغرافية
العنوان: Paracetamol toxicity in classic homocystinuria: Effect of N -acetylcysteine on total homocysteine.
المؤلفون: Elkhateeb N; Department of Metabolic Medicine Cambridge University hospitals NHS Foundation Trust Cambridge UK.; Department of Clinical Genetics Cambridge University hospitals NHS Foundation Trust Cambridge UK., Hyde S; Department of Gastroenterology Norfolk and Norwich University Hospital NHS Trust Norwich UK., Hogg SL; Biochemical Genetics Unit Cambridge University Hospitals NHS Foundation Trust Cambridge UK., Allsop D; Department of Histopathology Norfolk and Norwich University Hospitals NHS Trust Norwich UK., Shankar A; Department of Gastroenterology Norfolk and Norwich University Hospital NHS Trust Norwich UK., Deegan P; Department of Metabolic Medicine Cambridge University hospitals NHS Foundation Trust Cambridge UK., Tan CY; Department of Metabolic Medicine Cambridge University hospitals NHS Foundation Trust Cambridge UK.
المصدر: JIMD reports [JIMD Rep] 2023 Mar 03; Vol. 64 (3), pp. 238-245. Date of Electronic Publication: 2023 Mar 03 (Print Publication: 2023).
نوع المنشور: Case Reports
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: United States NLM ID: 101568557 Publication Model: eCollection Cited Medium: Print ISSN: 2192-8304 (Print) Linking ISSN: 21928304 NLM ISO Abbreviation: JIMD Rep Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2019- : [Hoboken, NJ] : Wiley
Original Publication: Berlin : SSIEM and Springer-Verlag, c2011.
مستخلص: Classical homocystinuria (HCU) is caused by cystathionine β-synthase deficiency leading to impaired homocysteine transsulfuration and accumulation of homocysteine and methionine. Patients present with a wide spectrum of manifestations including ocular, skeletal, neuropsychiatric, and vascular manifestations. We report a 48-year-old female with pyridoxine-unresponsive HCU treated with betaine, cyanocobalamin, and folate. Her diet was non-restricted due to intolerance of low-methionine diet. She was admitted to hospital following a fall, with multiple fractures and subsequently developed acute liver failure with encephalopathy. Shock, sepsis, and liver ischaemia/thrombosis were excluded. In the context of glutathione depletion expected in HCU, hepatic dysfunction was presumed to be due to iatrogenic paracetamol toxicity, despite paracetamol intake at conventional therapeutic dose, with role of hypermethioninemia as a contributing factor being uncertain. Betaine was discontinued on hospital admission. N -Acetylcysteine (NAC) infusion was initiated. Plasma total homocysteine (tHcy) was 3.4 μmol/L 9 days following initiation of NAC treatment with a markedly elevated plasma methionine of 1278 μmol/L. tHcy concentration returned to pre-admission baseline after NAC was discontinued. Recovery following this episode was slow with a prolonged cholestatic phase and gradual improvement in jaundice and coagulopathy. We recommend that paracetamol should be administered cautiously in HCU patients due to underlying glutathione depletion and risk of toxicity even at therapeutic doses. NAC is clearly effective in lowering tHcy in classical HCU in the short-term however further research is required to assess clinical efficacy and use as a potential therapy in classical HCU.
Competing Interests: The authors declare no conflict of interest.
(© 2023 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)
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فهرسة مساهمة: Keywords: N‐acetylcysteine; acute liver failure; classical homocystinuria; glutathione depletion; paracetamol toxicity; plasma total homocysteine
تواريخ الأحداث: Date Created: 20230508 Latest Revision: 20230815
رمز التحديث: 20230815
مُعرف محوري في PubMed: PMC10159864
DOI: 10.1002/jmd2.12363
PMID: 37151359
قاعدة البيانات: MEDLINE
الوصف
تدمد:2192-8304
DOI:10.1002/jmd2.12363