Why Infants with Some Inherited Metabolic Diseases do not Develop Neonatal Indirect Hyperbilirubinemia ? An Overlooked Detail

Aim: Although indirect hyperbilirubinemia is the most common neonatal problem in term newborns, it is rarely observed in newborns with some inherited metabolic diseases. Therefore, we aimed to compare the frequency of indirect hyperbilirubinemia in newborns with these diagnoses and compare them with healthy newborns. Materials and Methods: In the study group, term newborns with inherited metabolic diseases characterized by metabolic acidosis and/or hyperammonemia were included retrospectively and prospectively between January 1st, 2001, and December 31st, 2014. Healthy-term newborn infants were prospectively included in the control group. Results: In the study group (n=106), 63.2% of the patients had organic acidemia, 20.8% urea cycle disorders, 4.7% mitochondrial diseases, 5.7% fatty acid oxidation disorders, and 5.7% other diseases, while the control group included 126 healthy term newborns. Mean serum indirect bilirubin levels were significantly lower in the study group compared to the control group (5.8 +/- 5.4 mg/dL vs 13.9 +/- 4.1 mg/dL, p<0.00, respectively). The frequency of phototherapy was 11.3% in the study group and 23.8% in the control group (p<0.05). While the incidence of jaundice was significantly lower in organic acidemia, urea cycle disorder, and fatty acid oxidation disorders (p<0.05), there was no difference in mitochondrial disease compared to the control group (p>0.05).<br /> Conclusion: This was the first epidemiological study aiming to determine a very low incidence of neonatal jaundice in newborns with inherited metabolic diseases characterized by metabolic acidosis and/or hyperammonemia. The exact pathophysiological mechanism of this strikingly low incidence of indirect hyperbilirubinaemia in these newborns should be investigated with prospective biochemical, enzymatic, molecular, and genetic studies.