A case report of autosomal recessive methemoglobinemia in a child

Abstract: Methemoglobinemia is a rare hematologic disorder characterized by impaired oxygen delivery due to oxidation of hemoglobin iron from the ferrous (Fe 2+ ) to the ferric (Fe 3+ ) state, leading to elevated methemoglobin (MetHb) levels and cyanosis. We report the case of a 3-year-old female with a history of congenital cyanotic heart disease who presented with worsening cyanosis and was found to have a MetHb level of 49.3%. She responded initially to methylene blue therapy, but levels fluctuated over the following week. Whole-exome sequencing revealed a homozygous missense variant in the cytochrome b5 (CytB5) reductase 3 gene, consistent with autosomal recessive methemoglobinemia due to CytB5 reductase deficiency. The identified variant has not been previously reported and was classified as a variant of uncertain significance. This case underscores the importance of considering hereditary methemoglobinemia in children with unexplained cyanosis and persistent MetHb elevation. Genetic evaluation remains essential in suspected hereditary cases to inform prognosis, guide long-term care, and support family counseling.