Methemoglobinemia
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Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated
methemoglobin Methemoglobin (British: methaemoglobin) (pronounced "met-hemoglobin") is a hemoglobin ''in the form of metalloprotein'', in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin. Sometimes, it i ...
in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications may include
seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
and
heart arrhythmias Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
. Methemoglobinemia can be due to certain medications, chemicals, or food or it can be inherited from a person's parents. Substances involved may include
benzocaine Benzocaine, sold under the brand name Orajel amongst others, is an ester local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products f ...
,
nitrates Nitrate is a polyatomic ion with the chemical formula . Salts containing this ion are called nitrates. Nitrates are common components of fertilizers and explosives. Almost all inorganic nitrates are soluble in water. An example of an insoluble ...
, or
dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment a ...
. The underlying mechanism involves some of the iron in
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
being converted from the
ferrous In chemistry, the adjective Ferrous indicates a compound that contains iron(II), meaning iron in its +2 oxidation state, possibly as the divalent cation Fe2+. It is opposed to "ferric" or iron(III), meaning iron in its +3 oxidation state, such a ...
e2+to the
ferric In chemistry, iron(III) refers to the element iron in its +3 oxidation state. In ionic compounds (salts), such an atom may occur as a separate cation (positive ion) denoted by Fe3+. The adjective ferric or the prefix ferri- is often used to spe ...
e3+form. The diagnosis is often suspected based on symptoms and a low blood oxygen that does not improve with
oxygen therapy Oxygen therapy, also known as supplemental oxygen, is the use of oxygen as medical treatment. Acute indications for therapy include hypoxemia (low blood oxygen levels), carbon monoxide toxicity and cluster headache. It may also be prophylactica ...
. Diagnosis is confirmed by a
blood gas A blood gas test or blood gas analysis tests blood to measure blood gas tension values, it also measures blood pH, and the level and base excess of bicarbonate. The source of the blood is reflected in the name of each test; arterial blood gase ...
. Treatment is generally with
oxygen therapy Oxygen therapy, also known as supplemental oxygen, is the use of oxygen as medical treatment. Acute indications for therapy include hypoxemia (low blood oxygen levels), carbon monoxide toxicity and cluster headache. It may also be prophylactica ...
and
methylene blue Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...
. Other treatments may include
vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
, exchange transfusion, and
hyperbaric oxygen therapy Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...
. Outcomes are generally good with treatment. Methemoglobinemia is relatively uncommon, with most cases being acquired rather than genetic.


Signs and symptoms

Signs and symptoms of methemoglobinemia (methemoglobin level above 10%) include shortness of breath,
cyanosis Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...
, mental status changes (~50%), headache, fatigue,
exercise intolerance Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe pos ...
, dizziness, and loss of consciousness. People with severe methemoglobinemia (methemoglobin level above 50%) may exhibit
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s,
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
, and death (level above 70%). Healthy people may not have many symptoms with methemoglobin levels below 15%. However, people with co-morbidities such as
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
, cardiovascular disease, lung disease,
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, or who have abnormal hemoglobin species (e.g.
carboxyhemoglobin Carboxyhemoglobin (carboxyhaemoglobin BrE) (symbol COHb or HbCO) is a stable complex of carbon monoxide and hemoglobin (Hb) that forms in red blood cells upon contact with carbon monoxide. Carboxyhemoglobin is often mistaken for the compound form ...
, sulfhemoglobinemia or sickle hemoglobin) may experience moderate to severe symptoms at much lower levels (as low as 5–8%).


Cause


Acquired

Methemoglobinemia may be acquired. Classical drug causes of methemoglobinaemia include various
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s (
trimethoprim Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for ''Pneumocystis'' pneumonia in peop ...
,
sulfonamides In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
, and
dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment a ...
),
local anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general an ...
s (especially
articaine Articaine is a dental amide-type local anesthetic. It is the most widely used local anesthetic in a number of European countriesOertel R, Ebert U, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet. 1997 Dec;33(6):418. an ...
,
benzocaine Benzocaine, sold under the brand name Orajel amongst others, is an ester local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products f ...
,
prilocaine Prilocaine () is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Löfgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a topical ...
, and
lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
), and
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine In organic chemistry, an aromatic amine is an organic compound consisting of an aroma ...
dyes,
metoclopramide Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesoph ...
,
rasburicase Rasburicase (trade names Elitek in the US and Fasturtec in the EU) is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is kn ...
,
umbellulone Umbellulone is a headache-inducing monoterpene ketone found in the leaves of the tree ''Umbellularia californica'', sometimes known as the "headache tree". It is hypothesized to cause headaches by influencing the trigeminovascular system via TRPA ...
,
chlorate The chlorate anion has the formula ClO3-. In this case, the chlorine atom is in the +5 oxidation state. "Chlorate" can also refer to chemical compounds containing this anion; chlorates are the salts of chloric acid. "Chlorate", when followed by ...
s,
bromate The bromate anion, BrO, is a bromine-based oxoanion. A bromate is a chemical compound that contains this ion. Examples of bromates include sodium bromate, (), and potassium bromate, (). Bromates are formed many different ways in municipal drinki ...
s, and
nitrite The nitrite polyatomic ion, ion has the chemical formula . Nitrite (mostly sodium nitrite) is widely used throughout chemical and pharmaceutical industries. The nitrite anion is a pervasive intermediate in the nitrogen cycle in nature. The name ...
s. Nitrates are suspected to cause methemoglobinemia. In otherwise healthy individuals, the protective enzyme systems normally present in red blood cells rapidly reduce the methemoglobin back to hemoglobin and hence maintain methemoglobin levels at less than one percent of the total hemoglobin concentration. Exposure to exogenous oxidizing drugs and their metabolites (such as benzocaine, dapsone, and nitrates) may lead to an increase of up to a thousandfold of the methemoglobin formation rate, overwhelming the protective enzyme systems and acutely increasing methemoglobin levels. Infants under 6 months of age have lower levels of a key methemoglobin reduction enzyme ( NADH-cytochrome b5 reductase) in their red blood cells. This results in a major risk of methemoglobinemia caused by nitrates ingested in drinking water, dehydration (usually caused by gastroenteritis with diarrhea), sepsis, or topical anesthetics containing benzocaine or prilocaine resulting in
blue baby syndrome Blue baby syndrome can refer to conditions that cause cyanosis, or blueness of the skin, in babies as a result of low oxygen levels in the blood. This term has traditionally been applied to cyanosis as a result of: #Cyanotic heart disease, whi ...
. Nitrates used in agricultural fertilizers may leak into the ground and may contaminate well water. The current EPA standard of 10 ppm nitrate-nitrogen for drinking water is specifically set to protect infants.
Benzocaine Benzocaine, sold under the brand name Orajel amongst others, is an ester local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products f ...
applied to the gums or throat (as commonly used in baby
teething Teething is the process by which an infant's first teeth (the deciduous teeth, often called "baby teeth" or "milk teeth") appear by emerging through the gums, typically arriving in pairs. The mandibular central incisors are the first primary te ...
gels, or sore
throat lozenge A throat lozenge (also known as a cough drop, sore throat sweet, troche, cachou, pastille or cough sweet) is a small, typically medicated tablet intended to be dissolved slowly in the mouth to temporarily stop coughs, lubricate, and soothe irri ...
s) can cause methemoglobinemia.


Genetic

Due to a deficiency of the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
diaphorase I (
cytochrome b5 reductase Cytochrome-''b''5 reductase is a NADH-dependent enzyme that converts ferricytochrome from a Fe3+ form to a Fe2+ form. It contains FAD and catalyzes the reaction: In its b5-reducing capacity, this enzyme is involved in desaturation and elongati ...
), methemoglobin levels rise and the blood of met-Hb patients has reduced oxygen-carrying capacity. Instead of being red in color, the arterial blood of met-Hb patients is brown. This results in the skin of white patients gaining a bluish hue. Hereditary met-Hb is caused by a
recessive gene In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
. If only one parent has this gene, offspring will have normal-hued skin, but if both parents carry the gene, there is a chance the offspring will have blue-hued skin. Another cause of congenital methemoglobinemia is seen in patients with abnormal hemoglobin variants such as
hemoglobin M Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
(HbM), or hemoglobin H (HbH), which are not amenable to reduction despite intact enzyme systems. Methemoglobinemia can also arise in patients with
pyruvate kinase deficiency Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and ...
due to impaired production of
NADH Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
– the essential cofactor for diaphorase I. Similarly, patients with
glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
may have impaired production of another co-factor,
NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...
.


Pathophysiology

The affinity for oxygen of ferric iron is impaired. The binding of oxygen to methemoglobin results in an ''increased'' affinity for oxygen in the remaining heme sites that are in ferrous state within the same tetrameric hemoglobin unit. This leads to an overall reduced ability of the red blood cell to release oxygen to tissues, with the associated
oxygen–hemoglobin dissociation curve The oxygen–hemoglobin dissociation curve, also called the oxyhemoglobin dissociation curve or oxygen dissociation curve (ODC), is a curve that plots the proportion of hemoglobin in its saturated (oxygen-laden) form on the vertical axis against ...
therefore shifted to the left. When methemoglobin concentration is elevated in
red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...
, tissue hypoxia may occur. Normally, methemoglobin levels are <1%, as measured by the CO-oximetry test. Elevated levels of methemoglobin in the blood are caused when the mechanisms that defend against
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
within the red blood cell are overwhelmed and the oxygen carrying ferrous ion (Fe2+) of the
heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consisti ...
group of the hemoglobin molecule is oxidized to the ferric state (Fe3+). This converts hemoglobin to methemoglobin, resulting in a reduced ability to release oxygen to tissues and thereby hypoxia. This can give the blood a bluish or chocolate-brown color. Spontaneously formed methemoglobin is normally reduced (regenerating normal hemoglobin) by protective enzyme systems, e.g., NADH methemoglobin reductase ( cytochrome-b5 reductase) (major pathway), NADPH methemoglobin reductase (minor pathway) and to a lesser extent the ascorbic acid and glutathione enzyme systems. Disruptions with these enzyme systems lead to methemoglobinemia. Hypoxia occurs due to the decreased oxygen-binding capacity of methemoglobin, as well as the increased oxygen-binding affinity of other subunits in the same hemoglobin molecule, which prevents them from releasing oxygen at normal tissue oxygen levels.


Diagnosis

The diagnosis of methemoglobinemia is made with the typical symptoms, a suggestive history, low oxygen saturation on
pulse oximetry Pulse oximetry is a noninvasive method for monitoring a person's oxygen saturation. Peripheral oxygen saturation (SpO2) readings are typically within 2% accuracy (within 4% accuracy in 95% of cases) of the more accurate (and invasive) reading of ...
measurements (SpO2) and these symptoms (cyanosis and hypoxia) failing to improve on oxygen treatment. The definitive test would be obtaining either
CO-oximeter A CO-oximeter is a device that measures the oxygen carrying state of hemoglobin in a blood specimen, including oxygen-carrying hemoglobin (O2Hb), non-oxygen-carrying but normal hemoglobin (HHb) (formerly, but incorrectly, referred to as 'reduced' ...
or a methemoglobin level on an
arterial blood gas test An arterial blood gas (ABG) test, or arterial blood gas analysis (ABGA) measures the amounts of arterial gases, such as oxygen and carbon dioxide. An ABG test requires that a small volume of blood be drawn from the radial artery with a syringe an ...
. Arterial blood with an elevated methemoglobin level has a characteristic chocolate-brown color as compared to normal bright red oxygen-containing arterial blood; the color can be compared with reference charts. The SaO2 calculation in the arterial blood gas analysis is falsely normal, as it is calculated under the premise of hemoglobin either being
oxyhemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
or deoxyhemoglobin. However, co-oximetry can
distinguish The ruling made by the judge or panel of judges must be based on the evidence at hand and the standard binding precedents covering the subject-matter (they must be ''followed''). Definition In law, to distinguish a case means a court decides th ...
the methemoglobin concentration and percentage of hemoblobin. At the same time, the SpO2 concentration as measured by pulse ox is false high, because methemoglobin absorbs the pulse ox light at the 2 wavelengths it uses to calculate the ratio of oxyhemoglobin and deoxyhemoglobin. For example with a methemoglobin level of 30-35%, this ratio of light absorbance is 1.0, which translates into a false high SpO2 of 85%.


Differential diagnosis

Other conditions that can cause bluish skin include
argyria Argyria or argyrosis is a condition caused by excessive exposure to chemical compounds of the element silver, or to silver dust. The most dramatic symptom of argyria is that the skin turns blue or blue-grey. It may take the form of ''generalize ...
, sulfhemoglobinemia,
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
,
Amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrilla ...
-induced bluish skin pigmentation and
acrodermatitis enteropathica Acrodermatitis enteropathica is an autosomal recessive metabolic disorder affecting the uptake of zinc through the inner lining of the bowel, the mucous membrane. It is characterized by inflammation of the skin (dermatitis) around bodily openings ...
.


Treatment

Methemoglobinemia can be treated with supplemental oxygen and
methylene blue Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...
. Methylene blue is given as a 1% solution (10 mg/ml) 1 to 2 mg/kg administered intravenously slowly over five minutes. Although the response is usually rapid, the dose may be repeated in one hour if the level of methemoglobin is still high one hour after the initial infusion. Methylene blue inhibits
monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first ...
, and
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
toxicity can occur if taken with an SSRI (
selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...
) medicine. Methylene blue restores the iron in hemoglobin to its normal ( reduced) oxygen-carrying state. This is achieved by providing an artificial electron acceptor (such as methylene blue or flavin) for NADPH methemoglobin reductase (RBCs usually don't have one; the presence of methylene blue allows the enzyme to function at 5× normal levels). The NADPH is generated via the hexose monophosphate shunt. Genetically induced chronic low-level methemoglobinemia may be treated with oral methylene blue daily. Also,
vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
can occasionally reduce cyanosis associated with chronic methemoglobinemia, and may be helpful in settings in which methylene blue is unavailable or contraindicated (e.g., in an individual with G6PD deficiency). Diaphorase (cytochrome b5 reductase) normally contributes only a small percentage of the red blood cell's reducing capacity, but can be pharmacologically activated by exogenous cofactors (such as methylene blue) to five times its normal level of activity.


Epidemiology

Methemoglobinemia mostly affects infants under 6 months of age (particularly those under 4 months) due to low hepatic production of methemoglobin reductase. The most at-risk populations are those with water sources high in
nitrates Nitrate is a polyatomic ion with the chemical formula . Salts containing this ion are called nitrates. Nitrates are common components of fertilizers and explosives. Almost all inorganic nitrates are soluble in water. An example of an insoluble ...
, such as wells and other water that is not monitored or treated by a water treatment facility. The nitrates can be hazardous to the infants. The link between blue baby syndrome in infants and high nitrate levels is well established for waters exceeding the normal limit of 10 mg/L. However, there is also evidence that breastfeeding is protective in exposed populations.


Society and culture


Blue Fugates

The Fugates, a family that lived in the hills of Kentucky, had the hereditary form. They are known as the "Blue Fugates". Martin Fugate and Elizabeth Smith, who had married and settled near
Hazard, Kentucky Hazard is a list of Kentucky cities, home rule-class city in, and the county seat of, Perry County, Kentucky, Perry County, Kentucky, United States. The population was 5,263 at the 2020 Census. History Local landowner Elijah Combs, Elijah Comb ...
in around 1800, were both carriers of the
recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
methemoglobinemia (met-H) gene, as was a nearby clan with whom the Fugates descendants intermarried. As a result, many descendants of the Fugates were born with met-H.


Blue Men of Lurgan

The "blue men of
Lurgan Lurgan () is a town in County Armagh, Northern Ireland, near the southern shore of Lough Neagh. Lurgan is about south-west of Belfast and is linked to the city by both the M1 motorway and the Belfast–Dublin railway line. It had a population ...
" were a pair of Lurgan men suffering from what was described as "familial
idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...
methaemoglobinaemia" who were treated by Dr.
James Deeny James Andrew Donnelly Deeny (7 November 1906 – 3 April 1994) was the Chief Medical Adviser of the Republic of Ireland and a senior administrator in the World Health Organization. Background Deeny was born in Lurgan, County Armagh, the son of ...
in 1942. Deeny, who would later become the Chief Medical Officer of the
Republic of Ireland Ireland ( ga, Éire ), also known as the Republic of Ireland (), is a country in north-western Europe consisting of 26 of the 32 counties of the island of Ireland. The capital and largest city is Dublin, on the eastern side of the island. A ...
, prescribed a course of
ascorbic acid Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
and
sodium bicarbonate Sodium bicarbonate (IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation ( Na+) and a bicarbonate anion ( HCO3−) ...
. In case one, by the eighth day of treatments, there was a marked change in appearance, and by the twelfth day of treatment, the patient's complexion was normal. In case two, the patient's complexion reached normality over a month-long duration of treatment.


See also

*
Carbon monoxide poisoning Carbon monoxide poisoning typically occurs from breathing in carbon monoxide (CO) at excessive levels. Symptoms are often described as "flu-like" and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. Large e ...
*
Hemoglobinemia Hemoglobinemia (or haemoglobinaemia) is a medical condition in which there is an excess of hemoglobin in the blood plasma. This is an effect of intravascular hemolysis, in which hemoglobin separates from red blood cells, a form of anemia. Hemogl ...


References


External links

{{Diseases of RBCs Red blood cell disorders Autosomal recessive disorders Wikipedia medicine articles ready to translate