Unmasking Congenital Methemoglobinemia: Novel CYB5R Mutation Discovered in an Adult with Symptomatic Polycythemia

• DOI: 10.4274/tjh.galenos.2024.2024.0232
• Publication Date: 2024-08-09T12:04:01Z
• Authors: Amiya Ranjan Nayak; Pratyusha Gudapati; Swapnil Tripathi; Jasmita Dass; Pradeep Kumar; Mukul Aggarwal
• Keywords: Methemoglobinemia

To the editor, Methemoglobinemia is characterized by presence of elevated levels methemoglobin (metHb), a form hemoglobin with reduced oxygen-carrying capacity.The commonest cause congenital methemoglobinemia cytochrome b5 reductase (CYB5R) enzyme deficiency [1].The clinical presentation varies widely, ranging from asymptomatic cases to severe tissue hypoxia and cyanosis [2].A 29 years old male presented clinic complaints headache, fatigue exertional dyspnea for last 5 months.He denied any history recent drug intake or toxic substance exposure.Physical examination revealed lips nail beds an oxygen saturation 74% pulse oximetry on room air.Laboratory investigations demonstrated polycythemia 21 g/dL, hematocrit 63%.(Summarized in table 1) Echocardiography did not suggest evidence structural heart disease.Arterial blood gas (ABG) analysis 96.4% metHb level 52.5% (through spectrophotometry principle), confirming diagnosis methemoglobinemia.Clinical exome sequencing (CES) novel homozygous missense mutation exon CYB5R gene NM_000398.7:c.431G>T[p.Gly144Val], resulting substitution glycine valine at codon 144.(Figure Ascorbic acid was administered as treatment, leading symptomatic improvement repeat ABG showing 15.1%.The encodes reductase, essential reduction functional hemoglobin.Mutations leads accumulation subsequent hypoxia.Persistent stimulation erythropoiesis polycythemia.There are 2 types deficiency.In type I, affects only RBCs causes isolated methemoglobinemia.The patients usually apart cosmetic issues.Type II all tissues associated intellectual disability, developmental delay other neurological abnormalities life span [1].Thus, our patient fits into 1 variant, who stayed many It's possible that he might have experienced additional, unidentified insult led additional higher levels, ultimately becoming symptomatic.Nakata et al, reported similar case, diagnosed 79 age [3].Till now, around 80 pathogenic variants been described gene.The defect endemic some communities US Russia [2].The identified case (p.Gly144Val) results amino substitution, Arg58Gln, which predicted be probably damaging PolyPhen2 software deleterious SIFT software.This previously.However, nucleotide same coding region causing disease phenotype [3].Management primarily focuses reducing alleviating symptoms hypoxia.Phlebotomy recommended.Treatment options include intravenous methylene blue acute patients.High dose ascorbic can used ambulatory instances where contraindicated like G6PD [4].The mechanism involves ferric iron (Fe³⁺) ferrous (Fe²⁺).The typically ranges 500 mg 1g three four times daily [5].As u n c o r e t d p f without history, given acid.The choice medication dosing regimen should tailored patient.Chronic administration may lead formation sodium oxalate nephrolithiasis [6].