A 2-month-old girl with severe cyanosis was brought to the emergency department of a local hospital. Because an acute asthma attack was suspected, she was immediately prescribed oxygen therapy, corticosteroids, aerosol with β2-adrenergic agents, and steroids. The infant did not improve after treatment, and she was transferred to the Children's Hospital.
On arrival, the infant, the first child of an Italian nonconsanguineous couple and born at term after a noncomplicated pregnancy, was described as irritable. Physical examination showed a pale, cyanotic, and mottled baby. Local emergency room staff noted that the infant was dehydrated, dusky, and cold to the touch. Her temperature was 90°F and her oxygen saturation remained in the low 80s while on 100% oxygen by nasal cannula. The infant had tachycardia (between 150 and 195 beats/min) and tachypnea (60 breaths/min). On auscultation, pulmonary findings were normal. Abdominal examination showed no hepatomegaly, splenomegaly, or tenderness. Neurologic examination did not reveal any deficiency, and the bregmatic fontanel was normal.
The infant's weight was 4,720 g (10–25th percentile), length was 54 cm (10–25th percentile), and head circumference 39 cm (10–25th percentile). The growth charts show no failure to thrive. Laboratory tests showed increased leukocytes, normal platelet count, and normal concentrations of hemoglobin and hematocrit. An important finding was significant methemoglobinemia (30.4%) and profound hypoxia (20.4 mm Hg). Radiography and electrocardiography findings were normal.
According to her parents, the infant's skin color had become “grey” and she had been particularly irritable for a couple of weeks. For the first 2 weeks of life, the child was exclusively breast-fed. She was then artificially fed because breast milk was not available. The parents reported that at 4 weeks of age, the baby experienced constipation. A pediatrician whom they consulted suggested a conventional, adapted milk formula reconstituted with courgette soup (120 mL for six meals).
What is the diagnosis?
1. Eisenmenger syndrome
2. Blue baby syndrome
3. Ebstein anomaly
4. Deficit of very long-chain acyl dehydrogenase
6. Carbon monoxide intoxication
Blue baby syndrome. When a cardiorespiratory problem had been excluded, intoxication was suspected. The parents reported that the child was fed formula reconstituted with courgette soup to resolve constipation. In fact, the available data supported the final diagnosis of infant methemoglobinemia caused by the ingestion of concentrated vegetable soup (blue baby syndrome). Treatment with 0.1 mL/kg 1% methylene blue and 1 g vitamin C soon resolved the symptoms.
Accumulation of methemoglobin in red cells can occur for three reasons: 1) a dominantly inherited abnormality in hemoglobin that prevents the reduction of methemoglobin to hemoglobin; 2) a recessively inherited deficiency in the enzyme methemoglobin reductase; or 3) exposure to hemoglobin-oxidizing chemicals or drugs, such as nitrates or nitrites contained in water and in some vegetables (such as carrots, spinach, courgette, cauliflower, red beets), Xylocaine, or benzene derivatives.
Blue baby syndrome, known as infant methemoglobinemia, is not an infrequent condition. Infants younger than 6 months of age are particularly susceptible to methemoglobinemia because they have smaller amounts of a key enzyme, NADH-cytochrome b5 reductase, which converts methemoglobin back to hemoglobin (2). For more than 40 years, nitrates in drinking water have been believed to be a primary cause of infantile methemoglobinemia. Nonetheless (3–5), some cases of infantile methemoglobinemia have involved infants who became ill after being fed formula that was reconstituted with vegetable soup and nitrate-free water. Our case suggests not feeding infants with increased amounts of vegetable foods, such as carrots, courgette, spinach, red beets, and cauliflower, to resolve constipation, because doing so may be a risk factor, particularly in the first months of life, for severe methemoglobinemia (1,6).
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4. Keating JP, Lell ME, Strauss AW, et al. Infantile methemoglobinemia caused by carrot juice. N Engl J Med 1973; 288:824–6.
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6. Knobeloch L, Salna B, Hogan A, et al. Blue babies and nitrate-contaminated well water. Environ Health Perspect 2000; 108:675–8.