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Favism in a female newborn infant whose mother ingested fava beans before delivery


Carlo Corchia, MD, Antonio Balata, MD, Gian Franco Meloni, MD, and Tullio Meloni, MD
From the Department of Pediatrics and Neonatology, University of Sassari. Sassari, Italy

We describe a case of favism in a female newborn infant with glucose-6-phosphate dehydrogenase (G6PD) deficiency whose mother had ingested fava beans 5 days before delivery. At birth there were clinical and hematologic signs of hemolytic anemia, hemoglobinuria, and no blood group immunization. Study of the G6PD activity and 2-deoxy-glucose-6-phosphate utilization rate revealed that the infant and the mother were heterozygous for G6PD deficiency. ( J Pediatr 1995; 127:807-8)
F avism is characterized by anemia, jaundice, and hemoglobinuria; it may develop in subjects with glucose-6-phosphate dehydrogenase deficiency as a consequence of the ingestion of fresh, frozen, cooked, raw, or dried fava beans. Favism also has been reported in breast-fed infants whose mothers had eaten fava beans. 1 We report favism in a female newbom infant whose mother ingested dried fava beans 5 days before delivery.


2d-G6P 2-Deoxy-glucose-6-phosphate
G6PD Glucose-6-phosphate dehydrogenase

A 2-hour-old girl was referred to our neonatal unit because of anemia. She was born at 37 weeks of gestation by cesarean section, done because of fetal distress after an uncomplicated pregnancy. Apgar scores were 6 at 1 minute and 8 at 5 minutes. Birth weight was 2500 gm.

Physical examhlation revealed diffuse pallor and yellow sclerae. A grade 316 systolic heart murmur was audible. The abdomen was distended by an enlarged liver and spleen. Neurologic status and findings of the remainder of the examination were normal. Systolic blood pressure was 57 mm Hg. Laboratory data were as follows: hemoglobin, 73 gm/L; erythrocyte count, 1.9 x 10 l2 /L; hematocrit, 0.23; lcukocyte count, 32.8 x 10 9 /L with 10 nucleated red cells per 100 leukocytes; reticulocyte count, 0.09; Heinz bodies, 0.054; bilirubin concentration, 174µmol/L (10.2 mg/dl); sodium ion concentration, 141 mmol/L; potassiurn ion concentration, 4.3 mmol/L; calcium ion concentration, 1.84 mmol/L (7.4 mg/dl); blood group 0, Rh+; and negative Coombs test result. Arterial blood gas values were as follows pH 7.35; partial pressure of carbon dioxide,4.6 kPa (34.7 mm Hg); partial pressure of oxygen, 8.3 kPa (62.3 mm Hg); bicarbonate concentration, 18.8 mmol/L; and base excess, -5.8. Antibodies for congenital infections were absent. The G6PD activity in erythrocytes purified by cellulose column filtration 2 was 6.5 U/gm hemoglobin; haptoglobins were absent. Urine examination demonstrated hemoglobinuria.

The mother revealed that she had had a meal with cooked dried fava beans 5 days before birth; at the time of admission for delivcry, her hematologic values and urinalysis findings were within the normal ranges.

The infant underwent transfusion with 55 ml of compatible blood group, 0, Rh+ blood, after which the hematocrit was 0.60. Phototherapy was used to treat the hyperbilirubinemia; the highest value was reached on the fourh day of life (326 µmol/L; 19.1 mg/dl). Three days after admission the hematocrit was 0.56 and the reticulocyte count 0.16; hemoglobinuria was still present. After 2 more days the hematocrit was 0.56, the reticulocyte count was 0.19, and the hemoglobinuria had disappeared. The infant was discharged home on the eleventh day of life in good clinical condition.

Four months later the infant's hematologic data were as follows: erythrocyte count, 5.04 x 10 12 /L; hemoglobin concentration, 100 gm/L; hematocrit, 0.33; leukocyte count, 25 x 10 9 /L with a normal differential cell count; G6PD activity, 4.61 U/gm hemoglobin (normal concentration, 6.73 ± 2.10); and utilization rate of 2-deoxyglucose-6-phosphate, 13.15% (normal rate <6%). 3

Maternal blood group was 0 Rh+. The G6PD activity was 5.9 U/gm hemoglobin in the mother, 7.10 U/gm hemoglobin in the father, 0 and 5.4 U/gm hemoglobin, respectively, in -me mother's two brothers, and 4.68 U/gm hemoglobin in the matemal grandmother. The 2d-G6P utilization rate was 9% in the mother and 13% in the grandmother.

Favism was very frequent among the populations of the Mediterranean area, particularly in Sardinia, because of the high prevalence of G6PD deficiency and the large consumption of fresh fava beans. 4 In recent years, however, a marked decline of cases of favism has been observed after the introduction of G6PD screening during the neonatal period and the counseling of parents to avoid the exposure of G6PDdeficient children to oxidant substances. 5

Vicine and convicine, two metabolically inactive glycones, have been isolated from fava beans. They may be cleaved by intestinal ß-glucosidase to produce divicine and isouramil, which may be responsible for the hemolytic crises. 6 These substances lower the concentration of reduced glutathione in vitro. 7 It was hypothesized that G6PDdeficient subjects who have hemolytic crises may have higher concentrations of intestinal ß-glucosidase than subjects without hemolysis, but no difference in the mean activity of ß-glucosidase between normal and G6PD-deficient subjects, with or without favism, has been demonstrated. 8

We believe that this patient is the first in whom a favism crisis occurred in utero and the clinical signs were evident at birth. The diagnosis was established on the basis of the medical history, the hematologic values, the presence of hemoglobinuria, the utilization rates of 2d-G6P, and the study of the family for G6PD activity. Both the mother and the infant were heterozygotes.

Divicine and isouramil, released from fava beans ungested by the mother 5 days before delivery, may have reached the fetus through the placenta, producing the destruction of the G6PD-deficient erythrocytes. That the hemolytic crisis was clinically manifested only in the infant but not un the mother, although both of them were heterozygous for G6PD deficiency, in our opinion is related to the different body masses. This hypothesis is supported by the observation that the frequency of favism is higher in G6PD-deficient children (71%) than in adults (29%). 4 Children usually eat larger amounts of fava beans than adults in relation to body mass, with consequent higher concentrations of oxidizing substances in blood and a higher risk of hemolytic crises.

Our observation demonstrates that the tisk of favism extends into the intrauterine penod as well, and may threaten the life of the fetus. This event may be unexpected, because heterozygous G6PD-deficient women may have normal enzymatic activity and may go unidentified even after hematologic investigationS We recommend that all women living in high prevalence areas be counseled to avoid the ingestion of fava beans and exposure to other oxidizing substances during pregnancy.


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6. Mager J, Glaser G, Razin A, Izak G, Bien S, Noam M. Metabolic effects of pyrimidines derived from fava bean glycosides on human erythrocytes deficient in glucose-6-phosphate dehydrogenase. Biochem Biophys Res Commun 1965;20:35-40.
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8. Mareni C, Repello L, Forteleoni G, Meloni T, Gaelani GF. Favism: looking for an autosomal gene associated with glucose-6-phosphate dehydrogenase deficiency. J Med Genet 1984;21 :278-80.


Submitted for publication March 31, 1995;
accepted June 13, 1995.

Reprint requests: Tullio Meloni, MD,
Department of Pediatrics and Neonatology,
University of Sassari,
Viale S. Pietro 12,
07100 Sassari, Italy.