A female patient inherits congenital methemoglobinemia due to a novel homozygous CYB5R3 mutation and G6PD deficiency

Abstract

Methemoglobinemia is a disorder that can result from inherited or acquired etiologies. Congenital methemoglobinemia, being less common, can occur from autosomal recessive mutations in the enzyme cytochrome b5 reductase (CYB5R) or autosomal dominant mutations in the globin genes. We present a case of a 32-year-old woman with a lifelong history of cyanosis experiencing dyspnea for 5 hours after consuming cured sausages and dyeing her hair. She was admitted to hospital due to acute respiratory failure with an oxygen saturation of 80%. Physical examination revealed central and peripheral cyanosis. Arterial blood gas analysis showed a PaO₂ of 292 mmHg and SaO2 of 100%. The calculated oxygen saturation gap was 20%. Methemoglobin level was elevated at 36.9%. Other laboratory findings and peripheral blood smear were consistent with acute intravascular hemolysis from oxidative stress. The result of flow cytometry for glucose-6-phosphate dehydrogenase (G6PD) was compatible with G6PD deficiency. Direct DNA sequencing analysis identified a novel homozygous mutation, likely a pathogenic missense variant in the CYB5R3 gene, c.802_803delGAinsCC (p.Glu286Pro). The diagnosis in this patient encompasses acquired methemoglobinemia superimposed on congenital methemoglobinemia and acute hemolysis from G6PD deficiency. Because methylene blue is contra-indicated among patients with G6PD deficiency, treatment with N-acetylcysteine and supportive measures were initiated, resulting in symptom improvement in this patient.