Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (306 page)

   Loss of two loci results in α-thalassemia-1 trait (a
-thalassemia minor
). There are two variants, depending if the two affected genes are on the same chromosome, or one per chromosome. Adult patients may have a mild microcytic, hypochromic anemia. In these cases, the red cells are microcytic, hypochromic, and target cells are present. Hb electrophoresis is normal. Definitive diagnosis can only made by molecular genetic techniques.

   Loss of only one locus results in α-thalassemia-2 trait (α-
thalassemia minima
or silent carrier of α-thalassemia). There are no hematologic abnormalities, and Hb electrophoresis is normal. The diagnosis can only be made by DNA analysis.

   Hemoglobin Constant Spring is a common structural variant associated with α-thalassemia in Asia. It is associated with a normal α chain, but the Constant Spring allele functions as a severe α-thalassemia gene. Patients show a minor, very slowly migrating abnormal Hg component of Hg electrophoresis. Homozygosity results in a mild form of HbH disease.

   Couples at risk for having offsprings with homozygous thalassemia may choose
antenatal diagnosis
by direct gene analysis of the fetus.

Suggested Readings

Benz EJ. Newborn screening for α-thalassemia-keeping up with globalization.
N Engl J Med.
2011;364:770–771.

Forget BG. Thalassemia.
Hematol Clin North Am.
2010;24:1–140.

Rachmilewitz EA, Giardina PJ. How I treat thalassemia.
Blood.
2011;118:3479–3488.

   
HEMOLYTIC INTRINSIC RED BLOOD CELL DEFECTS

ENZYMOPATHIES

The most common enzymopathies are glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiencies. Other rare deficiencies of RBC enzymes do occur but will not be discussed here.

GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY

   Definition

G6PD deficiency is an X-linked inherited RBC enzyme deficiency. Incidence is high in regions where malaria is or was prevalent. More than 300 variants have been described. G6PD deficiency can be divided into three classes, with the normal genotype being designated G6PD type B.

   Class 1 (Mediterranean variant, also designated G6PD type B−): <5% of normal RBC enzyme activity. It results in a
chronic
hemolytic anemia exacerbated by oxidant drugs or febrile illnesses. Very severe hemolytic attacks develop after the ingestion of fava beans (
favism
).

   Class 2 (African variant, G6PD type A−): <10% of normal RBC enzyme activity; patients have
episodic
hemolytic attacks produced by certain infections, oxidant drugs, or diabetic ketoacidosis. It is not triggered by ingestion of fava beans.

   Class 3: 10–60% of the normal enzyme activity. There is no hemolysis except for limited episodes (2–3 days) after ingestion of oxidant drugs or following infections. Similar G6PD levels are found in female carriers.

   Who Should Be Suspected?

G6PD deficiency should be considered in the differential diagnosis of a patient with nonimmune (Coombs negative) hemolytic anemia.

   Laboratory Findings