Methemoglobinemia is a rare overlooked differential diagnosis in patients presented with
cyanosis and
dyspnea unrelated to cardiopulmonary causes. Our patient is 29 year old Indian non-smoker male, his story started 6 months prior to presentation to our center when he had generalized
fatigue and discoloration of hands. He presented with persistent
polycythemia with elevated
hemoglobin level. The patient was misdiagnosed in another center as
polycythemia and treated with
Imatinib. The diagnosis of PV was revisited and ruled out in view of negative JAK2, normal
erythropoietin level and absence of features of panmyelosis. Clinical
cyanosis and lowoxygen saturation in the presence of normal arterial
oxygen tension was highly suggestive of
methemoglobinemia. Arterial blood gas revealed a
methemoglobin level of 38% (normal: 0-1.5%).
Cytochrome B5 reductase (Methemoglobin reductase B) was deficient at level of <2.6 U/g Hb) (normal: 6.6-13.3), consistent with
methemoglobin reductase (
cytochrome b5) deficiency and hence the diagnosis of
congenital methemoglobinemia was established. The role of
Imatinib in provoking
methemoglobinemia is questionable and association between
Imatinib and
methemoglobinemia never described before. In our case, there were no other offending drugs in aggravating the patients' symptoms and
cyanosis. The patient started on
Vitamin C 500 mg once daily for which he responded well with less
cyanosis and significant reduction of
methemoglobin level.
Congenital methemoglobinemia is a rare underreported
hemoglobin disease and often clinically missed. Upon extensive review of English literature for cases of
congenital methemoglobinemia due to deficiency of
cytochrome b5 reductase, we found 23 cases diagnosed as type I (including the case reported here). 17 cases (~74%) of type I and 6 cases (27%) of type II. There is male predominance 73% versus 26% in females. Almost half of reported cases 12 cases (52%) are Indian, 2 Japanese, 3 English, 2 Arabic, one case Spanish and one case Italian. For type I, the median calculated age is 31 years with
cyanosis and
shortness of breath being the most common sign and symptoms. For type II: Six cases were reported in English literature, all in pediatric age group with median calculated age at presentation is 6 years with
neurologic manifestations and
mental retardation are the most common type II associated symptoms. Due to lack of systematic epidemiological studies,
congenital methemoglobinemia is under diagnosed as it is under investigated and usually overlooked especially when presenting in adulthood and in absence of obvious acquired agents.