title: Congenital methemoglobinemia due to NADH-methemoglobin reductase deficiency in three Indian families.
abstract: Congenital methemoglobinemia is a relatively rare clinical disorder characterized by life-long cyanosis, caused by either an inherited mutant hemoglobin (Hb-M) or deficiency of physiologically active NADH-dependent methemoglobin reductase (NADH-MR). NADH-MR deficiency leads to two different types of recessive congenital methemoglobinemia. In type I, cyanosis is the only major symptom and NADH-MR deficiency is restricted only to the red blood cells. In type II, cyanosis is associated with severe mental retardation and neurological impairment. The objective of this study is to establish the cause of cyanosis in our cases of congenital methaemoglobinemia. Erythrocyte NADH-MR activity was assayed spectrophotometrically. Spectral analysis of the hemolysate treated with potassium ferricyanide was recorded between 400-700 nm and Hb electrophoresis on starch gel at pH 7.0 was done to rule out the presence of Hb-M. NADH-MR deficiency was detected in 3 families. There was a history of consanguinity in one of these cases. The three propositi presented with breathlessness, fever and peripheral cyanosis. There was no history of cardiac illness or exposure to drugs and chemicals. There were no signs and symptoms of mental retardation. The presence of Hb-M was ruled out. Hb-A2, Hb-F, G6PD activity and reduced glutathione levels were normal. NADH-MR activity in all the cases ranged from 4.1 to 9.2 IU/g Hb (normal range 7.0-24.0 IU/g Hb). We describe NADH-MR deficiency in three unrelated cases (age 4 months to 6 years) where the activity of the enzyme was 30-40% of normal. These three cases of congenital methemoglobinemia are due to type-I NADH-MR deficiency without mental retardation.
authors.affiliation: Institute of Immunohaematology, (Indian Council of Medical Research), 13th Floor, New Multistoried Building, K.E.M. Hospital Campus, Parel, Mumbai 400012, India.
authors.forename: Prabhakar S
authors.initials: PS
authors.lastname: Kedar
authors.forename: Roshan B
authors.initials: RB
authors.lastname: Colah
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Dipika
authors.initials: D
authors.lastname: Mohanty
mesh_terms: D002648:Child; D003490:Cyanosis / Q000151:congenital / Q000201:enzymology / Q000235:genetics; D042966:Cytochrome-B(5) Reductase / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D008708:Methemoglobinemia / Q000151:congenital* / Q000201:enzymology* / Q000235:genetics; D010641:Phenotype
chemical_list: D042966:Cytochrome-B(5) Reductase