Congenital Recessive Methemoglobinemia Revealed in Adulthood: Description of a New Mutation in Cytochrome b5 Reductase Gene.
Methemoglobinemia can be acquired (oxidizing drugs or chemicals products) or inherited either by mutations affecting globin chains [M hemoglobins (M Hbs)] or by defects in the enzymatic system involved in the reduction of spontaneous Hb oxidation: nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase. It is encoded by the CYB5R3 gene: there are two phenotypes of autosomal recessive congenital methemoglobinemia, in type II CYB5R deficiency is generalized and affects all cells, leading to an early onset, whereas in type I, the enzyme deficiency is restricted to erythrocytes, usually discovered in infancy but not exclusively. We report a new case of methemoglobinemia discovered in a patient from Bahrain who exhibited an unknown dyspnea at the age of 37 years without trigger events or oxidizing products. We discovered a new mutation in the CYB5R3 gene: exon 9, codon 266 (delGAG) (GLU) (CYB5R3: c.726_729delGAG) in the homozygous state. Appearance of methemoglobinemia in an adult usually suggests an acquired cause but our case illustrated that it could also reveal a type I mutation of cytochrome b5 reductase.
a Service d'Onco Hématologie, Hôpital Saint Vincent de Paul , Lille , France.
Alexandra
A
Forestier
c Departement de Génétique , Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris , Créteil , France.|d Université Paris Est Créteil and Institut Mondor de Recherche Biomédicale , INSERM, Créteil , France.
Serge
S
Pissard
c Departement de Génétique , Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris , Créteil , France.
Justine
J
Cretet
a Service d'Onco Hématologie, Hôpital Saint Vincent de Paul , Lille , France.
Adeline
A
Mambie
a Service d'Onco Hématologie, Hôpital Saint Vincent de Paul , Lille , France.|b Université Catholique de Lille, Université Nord de France , Lille , France.
Laurent
L
Pascal
a Service d'Onco Hématologie, Hôpital Saint Vincent de Paul , Lille , France.|b Université Catholique de Lille, Université Nord de France , Lille , France.
Manuel
M
Cliquennois
a Service d'Onco Hématologie, Hôpital Saint Vincent de Paul , Lille , France.|b Université Catholique de Lille, Université Nord de France , Lille , France.
Nathalie
N
Cambier
a Service d'Onco Hématologie, Hôpital Saint Vincent de Paul , Lille , France.|b Université Catholique de Lille, Université Nord de France , Lille , France.
Christian
C
Rose
D000328:Adult; D003062:Codon; D003241:Consanguinity; D042966:Cytochrome-B(5) Reductase / Q000235:genetics*; D004252:DNA Mutational Analysis; D004909:Erythrocyte Indices; D005091:Exons; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D008708:Methemoglobinemia / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
D003062:Codon; D042966:Cytochrome-B(5) Reductase
Adulthood; congenital methemoglobinemia; cytochrome b5 reductase mutation