De Novo Occurrence of Hb Chile [β28(B10) Leu→Met] in a Korean Boy with Methemoglobinemia

Hemoglobin (Hb) Chile, a variant of Hb M, is produced by a point mutation of <i><u>C</u></i>TG→<i><u>A</u></i>TG on codon 29 (legacy codon 28) of the Hb β locus gene, which results in an amino acid substitution of Leu→Met. It has been identified in two families worldwide and is inherited in an autosomal dominant manner. Here, we report a case of Hb Chile in which a <i>de novo</i> mutation was detected in the proband. A 17-year-old male presented to the outpatient clinic with a pale appearance. There was cyanosis on his lips and fingers. Blood tests indicated the existence of hemolysis, but complete blood counts revealed no anemia. Peripheral arterial oxygen saturation on pulse oximetry was 80% on room air and did not improve with oxygen supplementation. The level of methemoglobin was 15.4%. Targeted next-generation sequencing identified a heterozygous NM_000518.4(<i>HBB</i>):c.85C > A mutation, indicating Hb Chile. The Hb Chile mutation, on the other hand, was not discovered in his parents, implying that it arose as a result of a <i>de novo</i> mutation. This case highlights the necessity of suspecting Hb gene mutations in patients with unexplained chronic methemoglobinemia, even if there is no family history.