A glance at transient hyperammonemia of the newborn: Pathophysiology, diagnosis, and treatment: A review

Abstract

Hyperammonemia is the excessive accumulation of ammonia in the blood, and is usually defined as a plasma level above 100 µmol/L in neonates or above 50 µmol/L in term infants, children, and adolescents. Patients with hyperammonemia usually experience life-threatening neuropsychiatric symptoms, especially newborns. It is routinely caused by inherited metabolic diseases and also by acquired disorders, such as liver failure, portosystemic shunting, gastrointestinal hemorrhage, ureterosigmoidostomy, renal tubular acidosis, hypoxic ischemic encephalopathy, infections with urea-metabolizing organisms, and some drugs. Transient hyperammonemia of the newborn (THAN) is a special type of hyperammonemia acknowledged in the field of metabolic disease as an inwell-defined or well-understood entity, which can be diagnosed only after the exclusion of genetic and acquired causes of hyperammonemia. Although the prognosis for THAN is good, timely identification and treatment are essential. Currently, THAN is underdiagnosed and much less is mentioned for early diagnosis and vigorous treatment. Herein, we present common themes that emerge from the pathogenesis, diagnosis, and management of THAN, based on current evidence. When a newborn presents with sepsis, intracranial hemorrhage, or asphyxia that cannot explain coma and seizures, doctors should always keep this disease in mind.

Hyperammonemia in the Pediatric Emergency Department

“…23 In contrast, transient hyperammonemia of the newborn can occur in infants, likely secondary to a transient deficiency of one of the enzymes in the urea cycle or a renal amino acid transport defect. 24 These patients can be either symptomatic or asymptomatic, though their neurologic outcomes tend to be favorable. 24 Finally, other inborn errors of metabolism can result in hyperammonemia.…”

“…24 These patients can be either symptomatic or asymptomatic, though their neurologic outcomes tend to be favorable. 24 Finally, other inborn errors of metabolism can result in hyperammonemia. Organic acidemias such as propionic acidemia, methylmalonic acidemia, and isovaleric acidemia are leading causes of hyperammonemia in newborns.…”

“…It is posited that hypoxic stress increases catabolism and decreases urea cycle activity, a combination that leads to hyperammonemia 23 . In contrast, transient hyperammonemia of the newborn can occur in infants, likely secondary to a transient deficiency of one of the enzymes in the urea cycle or a renal amino acid transport defect 24 . These patients can be either symptomatic or asymptomatic, though their neurologic outcomes tend to be favorable 24 …”

Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy

“…Hypoxic-ischemic damage in the kidneys causes renal failure with oliguria, leading to a water and electrolyte imbalance. Liver damage leads to hyperammonemia, coagulopathy, and other gastrointestinal dysfunctions, such as poor peristalsis [16,17]. Hematological abnormalities due to HIE include increased nucleated RBCs, thrombocytopenia, neutropenia or neutrophilia, and coagulopathy [18].…”