Discussion:
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most
prevalent blood cell disorder in humans [5]. It is an X-linked
genetic disorder caused by a defect in chromosome X (band X q28)
[6]. It is usually diagnosed when patients present with signs and
symptoms of hemolytic anemia, secondary to oxidative stress. It is
usually triggered by infections, fava beans, and certain medications
[7]. Various screening tests are available to detect G6PD
deficiency, and the diagnosis is usually confirmed by quantitative
measurement of nicotinamide adenine dinucleotide phosphate (NADPH)
[8]. Treatment of acute episodes of hemolysis is by transfusion and,
more importantly, elimination of the cause of oxidative stress[9].
Methemoglobinemia, on the other hand, is a disorder of hemoglobin where
ferrous (Fe2+) iron in heme is oxidized to the ferric
(Fe3+) state. It is usually acquired, secondary to
oxidative stress in the body, but can rarely be congenital [4].
Physiologically, various enzyme systems such as NADH methemoglobin
reductase, NADPH methemoglobin reductase, ascorbic acid, and glutathione
reductase systems keep a check on the accumulation of methemoglobin in
the blood [10]. However, there are instances where these mechanisms
are insufficient to counter the conversion of hemoglobin to
methemoglobin, consequently promoting an oxidative state in the body.
This can be either due to the overproduction of methemoglobin or under
conversion to hemoglobin due to unavailable enzyme mechanisms. The
former can be secondary to exposure to certain drugs, chemicals, or food
items, but can sometimes be hereditary [11]. Inability of enzyme
systems to counteract methemoglobin can be secondary to enzyme
deficiencies, such as G6PD deficiency.
Usually, the patients typically
have a low SPO2 on pulse oximeters but a falsely high
SPO2 on arterial blood gasses (ABG) [12]. The
treatment depends on the level of methemoglobin in the body and
symptoms. The first step is to immediately remove any possible
precipitator if present. The treatment of choice for symptomatic or
asymptomatic patients with a level of methemoglobin >30
percent is methylene blue (1-2mg/kg) [13]. Methylene blue is reduced
to leuko-methylene blue via NADPH dependent methemoglobin reductase.
This, in turn, reduces methemoglobin back to hemoglobin, hence
correcting the abnormality [14] [Figure 1].
Rarely, patients can present with co-occurrence of methemoglobinemia and
G6PD deficiency[3, 15-18] . In such cases, extreme caution is
required while administering methylene blue as they do not have
sufficient levels of NADPH to reduce it. Otherwise, a cascade of
oxidative hemolysis ensues secondary to underlying G6PD deficiency,
resulting in a vicious cycle of further methemoglobinemia [10].
The most frequent cause of this co-occurrence reported in the literature
is the ingestion of fava beans, which can induce methemoglobinemia as
well as potentiate G6PD deficiency simultaneously [3, 15-18]. All
the reported cases in the literature are male, with median age of 6
years (range 1 – 56). All them were newly diagnosed with G6PD
deficiency upon presentation with MethHgb. Median Hgb was 8gm/dL (4.6 –
9.9) and median MetHgb was 8 % (5.6 – 35). 1 patient (our patient)
received methylene blue, and 3 received Vitamin C. All of them recovered
and were discharged. Our patient was also male and had taken a full meal
consisting of fava beans before presenting. Although his methemoglobin
level was 5.6 percent, he was given methylene blue due to his symptoms,
which worsened his hemolytic anemia [Table 2].
Interestingly, our patient had a history of favism in the past without
developing any symptoms. Only this time, he ate a larger amount of fava
beans which led to hemolysis and methemoglobinemia. Hence, while
treating patients with methemoglobinemia one should be vigilant that a
history of fava beans ingestion without any symptoms does not rule out
G6PD deficiency. It in fact depends upon the number of beans ingested
over a certain period of time [19].