Browsing by Author "Ivanovski, Ana (57197844214)"

The preventability of acute lymphocytic leukemia during childhood is currently receiving great attention, as it is one of the most common cancers in children. Among the known risk factors so far are those affecting the development of gut microbiota, such as a short duration or absence of breastfeeding, cesarean section, a diet lacking in short-chain fatty acids (SCFAs), the use of antibiotics, absence of infection during infancy, and lack of pets, among other factors. Namely, it has been shown that iron deficiency anemia (IDA) and lack of vitamin D may cause intestinal dysbiosis, while at the same time, both increase the risk of hematological malignancies. The presence of IDA and vitamin D deficiency have been shown to lead to a decreased proportion of Firmicutes in stool, which could, as a consequence, lead to a deficit of butyrate. Moreover, children with IDA have increased blood concentrations of cadmium, which induces systemic inflammation and is linked to the onset of an inflammatory microenvironment in the bone marrow. Finally, IDA and Cd exposure increase fibroblast growth factor 23 (FGF23) blood levels, which in turn suppresses vitamin D synthesis. A lack of vitamin D has been associated with a higher risk of ALL onset. In brief, as presented in this review, there are three independent ways in which IDA increases the risk of acute lymphocytic leukemia (ALL) appearance. These are: intestinal dysbiosis, disruption of vitamin D synthesis, and an increased Cd load, which has been linked to systemic inflammation. All of the aforementioned factors could generate the appearance of a second mutation, such as ETV6/RUNX1 (TEL-AML), leading to mutation homozygosity and the onset of disease. ALL has been observed in both IDA and thalassemia. However, as IDA is the most common type of anemia and the majority of published data pertains to it, we will focus on IDA in this review. © 2024 by the authors.

The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liverdamage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well. © The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.