Clinical Information

Hemolytic disease may be associated with deficiency of erythrocyte enzymes. The most commonly encountered is a deficiency of glucose-6-phosphate dehydrogenase (G6PD).

The G6PD locus is on the X chromosome and, thus, G6PD deficiency is a sex-linked disorder. Affected males (hemizygotes) inherit the abnormal gene from their mothers who are almost always asymptomatic carriers (heterozygotes). More than 300 molecular variants of G6PD are known, and the clinical and laboratory features of G6PD deficiency vary accordingly. With some variants, there is chronic, life-long hemolysis, but much more commonly, the condition is asymptomatic and only results in susceptibility to acute hemolytic episodes, which may be triggered by some medications, ingestion of fava beans, viral, or bacterial infections.  It is also associated with neonatal  hyperbilirubinemia.

The major G6PD variants occur in specific ethnic groups. Thus, knowledge of the ethnic background of the patient is important. G6PD deficiency has very high frequency in Southeast Asians and is the most common cause of hemolytic disease of the newborn in Southeast Asian neonates.  It is also seen in persons of African and Mediterranean descent.

Rasburicase therapy is contraindicated in patients with G6PD deficiency. Deficiency can be assessed by enzymatic and/or genetic assays. If deficient status can be unambiguously assigned by genotyping, that is sufficient. However, due to the limitations of genetic testing, in most cases it is necessary to perform G6PD enzyme testing to assign G6PD status (adapted from Relling et al).(1)