Congenital Methemoglobinemia: First Confirmed Case in the Arab Population with a Novel Variant in the CYB5R Gene in the State of Qatar: A Case Report

Abstract

Methemoglobinemia (MetHb) is a rare hematological condition characterized by high methemoglobin levels in the blood. It happens when hemoglobin is oxidized, resulting in hypoxia and cyanosis, which may occur in inherited or acquired forms. Inherited or congenital methemoglobinemia is a rare autosomal recessive condition and has never been reported in the Arab population. Here we report a case of a 22-year-old Arab man with a positive family history who presented with bluish discoloration of the fingers and lips and was found to have methemoglobinemia. Genetic study on the patient and his family revealed compound heterozygous variants in the CYB5R3 Exon 5 c.431G>A p.Gly144Asp likely pathogenic variant and CYB5R3 Exon 9 c.871G>A p.Val291Met variant of unknown significance. We suggest that the novel c.871G>A p.Val291Met variant could be causative for methemoglobinemia.

Keywords:

• methemoglobinemia
• Arab
• Qatar

Abbreviations

MetHb, methemoglobinemia; CYB5R, cytochrome b₅ reductase; WES, whole exome sequencing; NADH, nicotinamide adenine dinucleotide; NADPH, nicotinamide adenine dinucleotide phosphate oxidase; Hb, hemoglobin; MCV, mean corpuscular volume.

Statement of Ethics

Written informed consent was obtained from our patient to allow the publication of information and images. Institutional approval was required for this case report. The case report was approved by the Hamad Medical Corporation’s Medical Research Center – IRB – under the number MRC-04-23-043.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This article was funded by Qatar National Library. Open Access funding was provided by the Qatar National Library.