[2] Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis).

[3] Signs and symptoms of methemoglobinemia (methemoglobin level above 10%) include shortness of breath, cyanosis, mental status changes (~50%), headache, fatigue, exercise intolerance, dizziness, and loss of consciousness.

However, people with co-morbidities such as anemia, cardiovascular disease, lung disease, sepsis, or who have abnormal hemoglobin species (e.g. carboxyhemoglobin, sulfhemoglobinemia or sickle hemoglobin) may experience moderate to severe symptoms at much lower levels (as low as 5–8%).

[7] Classical drug causes of methemoglobinemia include various antibiotics (trimethoprim, sulfonamides, and dapsone[8]), local anesthetics (especially articaine, benzocaine, prilocaine,[9] and lidocaine[10]), and aniline dyes, metoclopramide, rasburicase, umbellulone, chlorates, bromates, and nitrites.

[citation needed] Infants under 6 months of age have lower levels of a key methemoglobin reduction enzyme (NADH-cytochrome b5 reductase) in their red blood cells.

The current EPA standard of 10 ppm nitrate-nitrogen for drinking water is specifically set to protect infants.

[14][15] Due to a deficiency of the enzyme diaphorase I (cytochrome b5 reductase), methemoglobin levels rise and the blood of met-Hb patients has reduced oxygen-carrying capacity.

[citation needed] Methemoglobinemia can also arise in patients with pyruvate kinase deficiency due to impaired production of NADH  – the essential cofactor for diaphorase I.

[17] This leads to an overall reduced ability of the red blood cell to release oxygen to tissues, with the associated oxygen–hemoglobin dissociation curve therefore shifted to the left.

Elevated levels of methemoglobin in the blood are caused when the mechanisms that defend against oxidative stress within the red blood cell are overwhelmed and the oxygen carrying ferrous ion (Fe2+) of the heme 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.

Genetically induced chronic low-level methemoglobinemia may be treated with oral methylene blue daily.

Also, vitamin C 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).

[25][26] 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.

Deeny, who would later become the Chief Medical Officer of the Republic of Ireland, prescribed a course of ascorbic acid and sodium bicarbonate.