A retrospective study of adult patients with noncirrhotic hyperammonemia

Abstract

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

Hyperammonemia syndrome associated with Ureaplasma spp. Infections in immunocompromised patients and transplant recipients: A systematic review and meta‐analysis

“…A flowchart shows the search process and study selection (Figure 1). We identified 18 relevant articles, which met the inclusion criteria for qualitative synthesis, of which 13 were case reports 13,23–34 and 2 were case series 16,35 . Only 3 were included for meta‐analysis 15,17,36 …”

“…Three studies 29,31,34 reported using azithromycin, levofloxacin, and doxycycline to manage hyperammonemia syndrome in these patients. Based on 14 studies, 13,16,23–35 the median length of treatment for HS patients was 21 (range: 2–120) days. For those patients who were started on initial treatment with β‐lactam antibiotics ( n = 2), symptoms and ammonia levels of HS did not improve 23,28 .…”

“…However, potential adverse drug effects such as prolongation of corrected QT interval and drug‐drug interactions with maintenance immunosuppressant medications need to be strongly considered, particularly in the transplant population. Even with antimicrobial therapy, some patients failed to recover 16,28,35 . Antimicrobial‐resistant strains of Ureaplasma spp.…”

“…We identified 18 relevant articles, which met the inclusion criteria for qualitative synthesis, of which 13 were case reports 13,[23][24][25][26][27][28][29][30][31][32][33][34] and 2 were case series. 16,35 Only 3 were included for meta-analysis. 15,17,36…”

“…Even with antimicrobial therapy, some patients failed to recover. 16,28,35 Antimicrobial-resistant strains of Ureaplasma spp. are also a growing concern among neonates and can also potentially threaten immunocompromised patients with HS.…”