Cyanosis is a physical finding that can occur at any age but presents the greatest challenge when it occurs in the newborn. The cause is multiple, and it usually represents an ominous sign, especially when it occurs in association with
neonatal sepsis, cyanotic
congenital heart disease, and airway abnormalities.
Cyanosis caused by abnormal forms of
hemoglobin can also be life-threatening, and early recognition is mandatory to prevent unnecessary investigations and delay in management. Abnormal
hemoglobin, such as
hemoglobin M, is traditionally discovered by electrophoresis, so the newborn screen, which is mandatory in several states, is a useful tool for the diagnosis. Although acquired
methemoglobinemia, caused by environmental
oxidizing agents, is common, congenital deficiency of the innate reducing
enzyme is so rare that only a few cases are documented in the medical literature around the world. We present a neonate with
cyanosis as a result of congenital deficiency of the reduced
nicotinamide adenine dinucleotide-
cytochrome b5 reductase enzyme. This infant was found to be blue at a routine newborn follow-up visit.
Sepsis, structural
congenital heart disease, prenatal administration, and ingestion of
oxidant dyes were excluded as a cause of the
cyanosis by history and appropriate tests. Chocolate discoloration of arterial blood provided a clue to the diagnosis. A normal newborn screen and
hemoglobin electrophoresis made the diagnosis of
hemoglobin M unlikely as the cause of the
methemoglobinemia (Hb A 59.4%, A2 1.8%, and F 38.8%). Red blood cell
enzyme activity and
DNA analysis revealed a homozygous form of the
cytochrome b5 reductase enzyme deficiency. He responded very well to daily
methylene blue and
ascorbic acid administration, and he has normal growth and developmental parameters, although he shows an exaggerated increase in his
methemoglobin level with minor
oxidant stress such as
diarrhea.