(Favism, G6PD)

Prevalence: 0.5 to 26 % (around the Mediterranean sea) depending on the geographical area. Pharmacogenetic disease: the vast majority of patients affected are not symptomatic until they are exposed to an external agent that causes acute hemolytic anemia. X-linked transmission (Xq28) of a mutation of the G6PD gene. Hemizygous boys and homozygous girls fully express the deficit;  heterozygous or homozygous girls with partial inactivation of an X allele have an intermediate phenotype.  Glucose-6-phosphate-dehydrogenase catalyzes the first oxidation reaction of the phosphate pentoses pathway and produces NADPH. NADPH is an electron donor necessary for the biosynthesis of nucleic acids, fatty acids and steroids, and its reducing power is necessary to help the cells to eliminate oxidizing agents. As the erythrocytes do not contain a nucleus nor an endoplasmic reticulum, the only role of G6PD in these cells is to provide the NADPH needed for the 3 enzyme reactions that eliminate H2O2.

The normal glucose-6-phosphate-dehydrogenase level is 7-11 U/g of hemoglobin, and it decreases as red blood cells age.

More than 230  genetic variants are described  (A, A-, Andalus, Orissa, Campinas, Chatham, Nilgiri, etc ...) but the two main forms are:

-        type A: Africa (and North America), where 10-20 % of activity persists;

-        type B: Mediterranean region, more severe ("favism") because the activity varies from 0 to 5 %.

Depending on the severity of the deficiency, the affected subjects are categorized into four classes:

-        class I: severe deficiency (1 to 2 % residual enzyme activity). Cause of chronic hemolytic anemia

-        class II: intermediate deficiency (3-10 % enzymatic activity);

-        class III: moderate deficiency (10-40 % enzymatic activity)

-        class IV: normal activity.

The level of G6PD may be at the lower limit of normal immediately after a hemolytic attack because the presence of many reticulocytes can artificially increase the average level.

The G6PD deficiency may present as:

1)        acute hemolytic anemia, the most common presentation The acute hemolytic crises are triggered by some oxidative drugs (some antimalarials, sulfamides, painkillers), some foods (beans, foods rich in vitamin C) or bacterial infection. In case of dietary or pharmacological cause, the importance of hemolysis is dose-dependent.
Clinical picture: palor, jaundice, dark urine. Non-conjugated hyperbilirubinemia, and Heinz's intra-erythrocytic body  on the blood smear.

2)        chronic non-spherocytic hemolytic anemia (very rare).  Chronic jaundice with biliary lithiases. The risk of hemolytic  crises is present.

3)        neonatal jaundice. Poorly-known incidence. Probably very rare.

Anesthetic implications: 

avoid medications that can cause hemolytic attacks according to the table below (recommendations of the AFSSAPS). Paracetamol, ibuprofen and tramadol may be used as analgesics for several consecutive days. Increased risk of infection and sepsis.

References:

-        Youngster I, Arcavi L, Schechmaster R, Akayzen Y, Popliski H, Shimonov J, Beig S, Berkovitch M.
Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. 
Drug Safety  2010; 33:713-26. 

-        Najafi N, Van de Velde A, Poulaert J.
Potential risks of hemolysis after short-term administration of analgesics in children with glucose-6-phosphate dehydrogenase deficiency.
J Pediatr 2011; 159:1023-8

-        Luzzato L, Ally M, Notaro R.
Glucose-6-phosphate dehydrogenase deficiency.
Blood 2020 ; 136 :1225-40

Updated: January 2021