A NOVEL L218P MUTATION IN NADH-CYTOCHROME B5 REDUCTASE ASSOCIATED WITH TYPE I RECESSIVE CONGENITAL METHEMOGLOBINEMIA

Abstract

The presence of central cyanosis that is unrelated to cardiopulmonary causes alerts clinicians to a possible diagnosis of methemoglobinemia. Congenital methemoglobinemia due to deficiency of nicotinamide-adenine dinucleotide (NADH)-cytochrome b5 reductase (cb₅r) is an autosomal recessive disorder characterized by life long cyanosis. Here we report a six-year old boy who presented with central cyanosis and upon examination revealed a methemoglobin level of 19.0%. Sequencing the CYB5R3 gene identified a homozygous T→C transition at base c.653, which changed codon 218 from leucine to proline (L218P) in cb₅r protein. Treatment with ascorbic acid relieved the cyanosis and returned methemoglobin levels to normal.

Keywords:

• congenital methemoglobinemia
• cyanosis
• cytochrome b5 reductase deficiency