Glucose-6-phosphate dehydrogenase deficiency and Gilbert syndrome: a gene interaction underlies severe jaundice without severe hemolysis.

The authors describe the paradoxical clinical phenotype of an undetected severe hemolysis in parallel with the development of severe jaundice in a 13-year-old male suffering from a confirmed interaction of glucose-6-phosphate dehydrogenase deficiency (Mediterranean variant, 563 C/T) and Gilbert syndrome [variant (TA)7/(TA)7]. The child had 2 acute hemolytic episodes at the age of 10 and 13 years following infections of unknown origin. Both episodes were characterized by considerably high bilirubin levels (1st episode: 10.8 mg/dL, 2nd episode: 17.8 mg/dL) associated with unexpectably mild hemolysis indices (1st episode hemoglobin levels, 11.1 g/dL; reticulocyte counts, 2.5%; 2nd episode hemoglobin values, 12.7 g/dL; reticulocyte counts, 2.5%). During the steady-state condition of the child, hemoglobin values were within the normal ranges for his age (14.2 g/dL) and bilirubin levels were slightly elevated (1.70 mg/dL, indirect 1.5 mg/dL). The interaction of the two genetic abnormalities in the causation of this odd clinical phenotype is discussed.