sodium-benzoate and Syndrome

Hyperammonemia is a rare, often fatal complication after transplantation. The etiology is unknown, but recognition and rapid treatment may help to improve the survival of this unusual syndrome. We present the largest case series to date of hyperammonemia after lung transplantation (LTx) and discuss a treatment protocol that has been developed at our institution.. We conducted a retrospective cohort series of patients who underwent LTx between January 1, 2000, and December 31, 2013. Patients who developed hyperammonemia syndrome in the posttransplantation period, which was defined as symptoms of encephalopathy and plasma ammonia level exceeding 200 μmol/L on at least 1 occasion, were included. Data including demographics, antimicrobial and immunosuppression regimens, ammonia levels and other pertinent laboratory data, treatments administered, and outcomes were recorded.. Eight of 807 lung transplant recipients developed hyperammonemia syndrome postoperatively during this time period. Median time to onset was 9.0 days, and median peak ammonia level was 370 μmol/L. All 8 patients were treated with hemodialysis, 7 of 8 patients were treated with bowel decontamination, and 5 of 8 patients were treated with nitrogen scavenging agents. Six of the 8 patients died.. The incidence of hyperammonemia syndrome in LTx patients was approximately 1%. Future research is needed to determine the efficacy of treatment, including hemodialysis, bowel decontamination, antibiotics, and the use of nitrogen scavenging agents in lung recipients with hyperammonemia.

Topics: Aged; Ammonia; Arginine; Biomarkers; Carnitine; Combined Modality Therapy; Decontamination; Female; Humans; Hyperammonemia; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Missouri; Phenylacetates; Protective Agents; Renal Dialysis; Retrospective Studies; Sodium Benzoate; Syndrome; Time Factors; Treatment Outcome; Up-Regulation

Citrullinemia type I (CTLN1, OMIM# 215700) is an inherited urea cycle disorder that is caused by an argininosuccinate synthetase (ASS) enzyme deficiency. In this report, we describe two spontaneous hypomorphic alleles of the mouse Ass1 gene that serve as an animal model of CTLN1. These two independent mouse mutant alleles, also described in patients affected with CTLN1, interact to produce a range of phenotypes. While some mutant mice died within the first week after birth, others survived but showed severe retardation during postnatal development as well as alopecia, lethargy, and ataxia. Notable pathological findings were similar to findings in human CTLN1 patients and included citrullinemia and hyperammonemia along with delayed cerebellar development, epidermal hyperkeratosis, and follicular dystrophy. Standard treatments for CTLN1 were effective in rescuing the phenotype of these mutant mice. Based on our studies, we propose that defective cerebellar granule cell migration secondary to disorganization of Bergmann glial cell fibers cause cerebellar developmental delay in the hyperammonemic and citrullinemic brain, pointing to a possible role for nitric oxide in these processes. These mouse mutations constitute a suitable model for both mechanistic and preclinical studies of CTLN1 and other hyperammonemic encephalopathies and, at the same time, underscore the importance of complementing knockout mutations with hypomorphic mutations for the generation of animal models of human genetic diseases.

Topics: Alleles; Animals; Arginine; Argininosuccinate Synthase; Blotting, Western; Cell Movement; Cerebellum; Citrullinemia; Developmental Disabilities; Disease Models, Animal; Female; Growth Disorders; Humans; Hyperammonemia; Immunoenzyme Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Mutation, Missense; Nitric Oxide; Phenotype; Sodium Benzoate; Syndrome