Abstract
Deficiency of NADH-cytochrome b5 reductase is the rare cause of recessive congenital methemoglobinemia (RCM) Type-II. It is associated with the mild cyanosis and mental retardation. We have identified three new patients with RCM type-II due to NADH-cytb5r deficiency due and also offered the prenatal diagnosis. All three index cases had cyanosis with severe progressive neurological dysfunction. Methemoglobin level was found in the range of 34.0% to 65% and red blood cell NADH-cytb5r activity were detected only 5 to 30% of normal. The clinical pictures were very similar in all three cases, with severe encephalopathy, microcephaly, generalized dystonia, movement disorders and severe cyanosis. The neurological prognoses are poor; in particular, all the patients do not walk or speak. DNA sequencing result identified two novel mutations. In the first case identified homozygous 2-bp deletion in exon 7 of the CYB5R3 gene, noted as c.604_605delCT (p.Thr202SerfsX98) and in the second case also discovered frame shift homozygous 3-bp deletion mutations (c.766_768delGAG) in exon 9 result in loss of Glutamic acid at codon 256. Third cases showed splice site homozygous mutation (p.Gly76Ser) first time associated with RCM II. Prenatal diagnosis of the fetus in this family revealed same homozygous mutation p.Gly76Ser.
Keywords: Recessive congenital methemoglobinemia (RCM) type II, NADH-cyb5r deficiency, Neurological disorders.
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Corresponding Author
Dr Prabhakar S Kedar, PhD
Scientist D, National Institute of Immunohaematology, Indian Council of Medical Research
13th Floor, New Multistoried Building, K.E.M Hospital Campus, Parel, Mumbai 400012, India
Tel: + 9122 24138518, Fax: + 9122 24138521, Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
DOI: https://dx.doi.org/10.18535/jmscr/v6i6.105
