Congenital methemoglobinemia caused by Hb-MRatnagiri (beta-63CAT-->TAT, His-->Tyr) in an Indian family.
Hb-M is a very rare hemoglobinopathy in the Indian subcontinent. We report a family with Hb-M with lifelong cyanosis from the Ratnagiri district in western India. The propositus was a 11-year-old female child with a history of increasing cyanosis exacerbated by fever and weakness. Similar complaints were also noted in her mother and five maternal family members. There was no history of cardiac illness or exposure to drugs and chemicals. The methemoglobin level was 39.3% in the propositus and 21.1% in her mother with normal NADH-methemoglobin reductase activity. Abnormal absorption peaks by spectroscopic analysis, presence of hemoglobin instability, and a slow-moving band on starch gel electrophoresis supported the presence of Hb-M. Automated DNA sequence analysis of the beta globin gene showed a C-->T substitution at codon 63. This leads to a substitution of histidine (CAT) by tyrosine (TAT) at the beta 63 (E7) position, similar to Hb-M Saskatoon. We have named this variant as Hb-M(Ratnagiri).
Kedar
Prabhakar S
PS
Institute of Immunohaematology, Indian Council of Medical Research, K.E.M. Hospital, Parel, Mumbai 400012, India.
Nadkarni
Anita H
AH
Phanasgoankar
Supriya
S
Madkaikar
Manisha
M
Ghosh
Kanjaksha
K
Gorakshakar
Ajit C
AC
Colah
Roshan B
RB
Mohanty
Dipika
D
D019943:Amino Acid Substitution; D002648:Child; D002908:Chronic Disease; D003490:Cyanosis / Q000151:congenital / Q000209:etiology / Q000235:genetics; D003596:Cytosine; D004247:DNA / Q000235:genetics; D005260:Female; D005914:Globins / Q000235:genetics*; D006449:Hemoglobin M / Q000235:genetics*; D006639:Histidine; D006801:Humans; D007194:India; D008708:Methemoglobinemia / Q000150:complications / Q000151:congenital*; D010375:Pedigree; D013941:Thymine; D014443:Tyrosine
C502787:hemoglobin M(Ratnagiri); D014443:Tyrosine; D006639:Histidine; D003596:Cytosine; D005914:Globins; D004247:DNA; D006449:Hemoglobin M; D013941:Thymine