Neonatal hyperammonemia: the evolution of views on pathogenesis, diagnosis and treatment

Background. Neonatal hyperammonemia is a condition caused by an increased content of ammonia in the blood of a newborn, both as a result of certain hereditary metabolic diseases and occurring against the background of severe pathology of the perinatal period. Neonatal hyperammonemia is defined as serum ammonia concentration exceeding 100 μmol/L for full-term infants and exceeding 150 μmol/L for preterm infants. A level exceeding 360 μmol/L (600 micrograms per deciliter (mcg/dL)) is considered a critical threshold, which is associated with a high risk of irreversible changes in the brain, liver, kidneys and other organ systems, and requires immediate initiation of extracorporeal detoxification methods. Upon entering the central nervous system, ammonia triggers a cascade of pathological reactions. The pivotal event in this case will be the overproduction of glutamine in astroglia. The relevance of neonatal hyperammonemia is underscored not only by its life-threatening nature and by the complexity of timely diagnosis due to the non-specific clinical presentation, but also by a significant risk of multiple organ failure and fatal outcome in the case of the delayed correction of hyperammonemia. Regardless of the cause, neonatal hyperammonemia can become life-threatening and lead to irreversible damage to cells of the central nervous system, liver and other organs.

Results. This review analyzes the current understanding of the etiopathogenesis of neonatal hyperammonemia, including the mechanisms of neuro- and cytotoxicity, the classification of etiological factors, and clinical semiotics. Special attention is paid to the differential diagnostic algorithm, which makes it possible to distinguish between primary defects of the urea cycle, organic acidemia and transient conditions. Intensive care protocols, including pharmacological methods of ammonia binding, indications for extracorporeal detoxification, and a long-term patient management strategy are considered in detail. It is emphasized that the outcome of the disease is directly determined by the timeliness of diagnosis and the immediate initiation of pathogenetic therapy.

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