Neonatal jaundice and glucose-6-phosphate dehydrogenase

Leite, Amauri Antiquera

doi:10.1590/S1516-84842010000600002

Abstracts

Glucose-6-phosphate dehydrogenase in newborn babies may be responsible for neonatal jaundice. There is a concern of many authors from other countries in respect to complications in neonates with hyperbilirubinemia; some authors even propose screening for glucose-6-phosphate dehydrogenase deficiency in newborn babies. A scientific report on this subject is published in this issue.

Glucosephosphate dehydrogenase deficiency; Jaundice, neonatal; Infant, newborn

A deficiência de glicose-6-fosfato desidrogenase em neonatos pode ser a responsável pela icterícia neonatal. Este comentário científico é decorrente do relato sobre o tema publicado neste fascículo e que preocupa diversos autores de outros países em relação às complicações em neonatos de hiperbilirrubinemia, existindo inclusive proposições de alguns autores em incluir o teste para identificar a deficiência de glicose-6-fosfato desidrogenase nos recém-nascidos.

Deficiência de glucosefostato desidrogenase; Ictericia neonatal; Recem-nascido

SCIENTIFIC COMMENTARIES

Clinical Analysis Department, Faculdade de Ciências Farmacêuticas - UNESP, Araraquara (SP), Brazil

Correspondence

ABSTRACT

Glucose-6-phosphate dehydrogenase in newborn babies may be responsible for neonatal jaundice. There is a concern of many authors from other countries in respect to complications in neonates with hyperbilirubinemia; some authors even propose screening for glucose-6-phosphate dehydrogenase deficiency in newborn babies. A scientific report on this subject is published in this issue.

Keywords: Glucosephosphate dehydrogenase deficiency; Jaundice, neonatal; Infant, newborn

The metabolism of the erythrocyte is very interesting because of the peculiarities of this cell with no nucleus. Its main function is to transport oxygen to tissues but without consuming it. Thermal energy is attained by the oxidation of glucose via the anaerobic pathway, which, although not very efficient or productive, is enough to meet its needs, especially to maintain the cell's biconcave shape. To obtain reducer energy, the red blood cell needs to divert 10% of the glucose consumed to the pentose phosphate cycle, with this being its only source of NADPH.

Through the pentose cycle, glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzymes reduce the nicotinamide adenine dinucleotide phosphate (NADP) coenzyme to its reduced form, NADPH, which is then used to maintain glutathione in its reduced state (GSH) by glutathione reductase. This pathway plays an important role in protecting red blood cells against the damage caused by oxidative stress, which is responsible for reducing the average life of erythrocytes.^(1-3)

For G6PD-deficient erythrocytes, a drop in the reduction of NADP to NADPH leads to a low potential reducer. This interferes in the metabolic oxidation of the organism, making it vulnerable to hemolysis by failing to protect the sulfhydryl groups in hemoglobin from Heinz body formation. In turn oxidation of the red cell membrane may lead to varying intensities of hemolytic crises and neonatal jaundice after the ingestion of certain oxidizing drugs, and during infectious and oxidizing processes.^(1,4)

The most serious consequence of G6PD deficiency is severe neonatal jaundice, which can lead to kernicterus. It is commonly believed that hyperbilirubinemia is a consequence of hemolysis, but in reality the level of hemoglobin and the reticulocyte count in infants are usually normal and, with the use of modern techniques, it has been shown that there is only a modest and inconsistent shortening of the life span of red blood cells which may, to a limited extent, contribute to jaundice. The main cause of neonatal jaundice in G6PD-deficient infants is the inability of the liver to conjugate bilirubin properly, thereby exacerbating the bilirubinemia.⁽⁵⁾

The study by Iglessias et al.⁽⁶⁾ presented in this issue shows that 3.0% of newborn males are G6PD deficient with one third of them suffering jaundice within 48 hours of life and bilirubin levels remaining higher than 10 mg/dL. The most serious case occurred in a neonate with mild G6PD deficiency but with intense and prolonged bilirubin, suggesting that other factors are associated with hemolysis, as has previously been discussed. Other studies have also reported the frequency of G6PD deficiency ranging from 2 to 3% in the Brazilian population.^(6-11) Thus these data suggest that 6 million Brazilians have G6PD deficiency and that 1% of infants had episodes of jaundice to varying degrees associated to G6PD deficiency; 1.9 million Brazilians ran the risk of severe neonatal jaundice with a risk of kernicterus.

The latest unofficial report on kernicterus in the United States suggests that at least 21% of children with kernicterus have documented G6PD deficiency.⁽¹²⁾

These facts led Beutler⁽¹³⁾ to ask a series of reflective questions and proposals. Should all newborns be screened? Is the human and financial cost worth it? Should this screening be limited to ethnic groups that are known to have high frequencies of the gene and if so, how will they be identified? Or would it be better simply to monitor bilirubin levels in newborns more closely, thus sparing them the tragedy of kernicterus, whatever the cause?

References

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