Familial idiopathic methemoglobinemia revisited: original cases reveal 2 novel mutations in NADH-cytochrome b5 reductase

Blood. 2002 Nov 15;100(10):3447-9. doi: 10.1182/blood-2002-05-1405. Epub 2002 Jul 5.

Abstract

In 1943, the first description of familial idiopathic methemoglobinemia in the United Kingdom was reported in 2 members of one family. Five years later, Quentin Gibson (then of Queen's University, Belfast, Ireland) correctly identified the pathway involved in the reduction of methemoglobin in the family, thereby describing the first hereditary trait involving a specific enzyme deficiency. Recessive congenital methemoglobinemia (RCM) is caused by a deficiency of reduced nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase. One of the original propositi with the type 1 disorder has now been traced. He was found to be a compound heterozygote harboring 2 previously undescribed mutations in exon 9, a point mutation Gly873Ala predicting a Gly291Asp substitution, and a 3-bp in-frame deletion of codon 255 (GAG), predicting loss of glutamic acid. A brother and a surviving sister are heterozygous; each bears one of the mutations. Thirty-three different mutations have now been recorded for RCM. The original authors' optimism that RCM would provide material for future genetic studies has been amply justified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cytochrome Reductases / deficiency
  • Cytochrome Reductases / genetics*
  • Cytochrome-B(5) Reductase
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Humans
  • Male
  • Methemoglobinemia / enzymology*
  • Methemoglobinemia / etiology
  • Methemoglobinemia / genetics
  • Molecular Sequence Data
  • Mutation*
  • Pedigree

Substances

  • Cytochrome Reductases
  • Cytochrome-B(5) Reductase