A retrospective study of adult patients with noncirrhotic hyperammonemia.

Autor: Stergachis AB; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Mogensen KM; Department of Nutrition, Brigham and Women's Hospital, Boston, Massachusetts, USA., Khoury CC; Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Lin AP; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Peake RW; Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Baker JJ; Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Barkoudah E; Hospital Medicine Unit, Division of General Internal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sahai I; Division of Medical Genetics and Metabolism, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sweetser DA; Division of Medical Genetics and Metabolism, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Berry GT; Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Krier JB; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2020 Nov; Vol. 43 (6), pp. 1165-1172. Date of Electronic Publication: 2020 Aug 16.
DOI: 10.1002/jimd.12292
Abstrakt: Adult-onset noncirrhotic hyperammonemia (NCH) is poorly understood and has a high morbidity and mortality. To elucidate the etiology and management of NCH, we performed a retrospective analysis of 23 adults (median age 51) with NCH treated between 2014 and 2020 at two academic medical centers. Hyperammonemia was diagnosed in all cases during the evaluation of altered mental status, with 22% presenting with seizures. Peak ammonia levels were >200 μmol/L in 70% of cases. Defects in ammonia metabolism were assessed using urea cycle biochemical testing, germline genetic testing, and testing for urease-producing infectious agents. Ammonia metabolism defects in these cases appear attributable to four major sources: (a) infection with urease-producing organism (n = 5); (b) previously undiagnosed inborn errors of metabolism (IEMs) (n = 4); (c) clinical exposures causing acquired urea cycle dysfunction (n = 6); and (d) unexplained acquired urea cycle dysfunction (uaUCD) (n = 8), as evidenced by biochemical signatures of urea cycle dysfunction without a genetic or clinical exposure. Severe protein malnutrition appeared to be a reversible risk factor for uaUCD. Overall, 13% of our cohort died prior to resolution of hyperammonemia, 26% died after hyperammonemia resolution, 57% survived after having reversible neurological changes, and 4% survived with irreversible neurological changes. Renal replacement therapy for ammonia clearance was often utilized for patients with an ammonia level above 250 μmol/L and patients were frequently empirically treated with antibiotics targeting urea-splitting organisms. Our study demonstrates that acquired urea cycle dysfunction, IEMs and urease-producing infections are major sources of adult-onset NCH and highlights successful management strategies for adult-onset NCH.
(© 2020 SSIEM.)
Databáze: MEDLINE
Externí odkaz: