Diagnostics of Inherited Metabolic Diseases in Newborns with the Hyperammonemia Syndrome at the Onset of Disease (Pilot Study)

The aim of the study was to develop a diagnostic model that allows with a high degree of probability predicting the development of inherited metabolic disease (IMD) in newborns with the hyperammonemia syndrome at the onset of disease and determine the adequate management tactics for such patients. Materials and Methods. The study included 15 female and 5 male infants with the hyperammonemia syndrome. All the patients underwent a full range of clinical laboratory studies in accordance with the standards of treatment of the underlying disease. Blood ammonia measuring (quantitative assessment) was carried out on the basis of the biochemical laboratory of the Children's City Clinical Hospital No.1 (Nizhny Novgorod, Russia) using a portable PocketChem BA blood ammonia meter (Japan) and Ammonia Test Kit II test strips (Japan) in accordance with the manufacturer's protocol. The confirmation of the IMD diagnosis was carried out using the tandem mass spectrometry (TMS) method and molecular genetic testing (genome sequencing). To check the assumptions, all the patients during the follow-up were randomized retrospectively into two groups depending on the TMS results and molecular genetic testing. Group 1 (n=8) included the patients diagnosed with IMD and group 2 (n=12) included the patients with transient hyperammonemia in the neonatal period. Results. The clinical manifestations of the hyperammonemia syndrome in the neonatal period are most frequently realized in the form of a syndrome of CNS depression of varying degrees up to coma (75%), a convulsive syndrome (55%), vomiting (40%) without significant differences in the frequency of occurrence due to the causes of hyperammonemia. In a third of cases, the onset of the hyperammonemia syndrome occurs in the early neonatal period. The ammonia levels in patients with hyperammonemia caused by IMD are statistically significantly higher than those in patients with transient hyperammonemia (p=0.014) which may serve as the first diagnostic sign of IMD in a newborn. A tendency to a more frequent development of anemia in infants with IMD (p=0.084) has been established which might be due to the compensation of metabolic acidosis. The presence of anemia in combination with clinical features and the level of hyperammonemia increases the risk of IMD. In the course of the study, a diagnostic model was developed for predicting the risk of IMD development in a newborn at the onset of hyperammonemia. Through the discriminant analysis, a statistically significant relationship was established between the level of ammonia at the onset, blood glucose and base deficiency levels, blood lactate, hemoglobin, erythrocyte levels, the average volume of erythrocytes and the pH level (p=0.040) with the risk of IMD development. The sensitivity of the model has amounted to 87.5%, the specificity - 83.3%. The diagnostic efficiency of the model is 85.0%. Conclusion. The proposed model can be used at detecting the debut of the hyperammonemia syndrome in newborns in order to predict the probability of IMD and work out the adequate tactics of the management for these patients.