We have characterized a new abnormal
hemoglobin (Hb) at position 32 of the
alpha-globin chain. The proband, a 38-year-old woman of Surinamese Black ancestry, was referred to the Academic Hospital in Amsterdam, The Netherlands, after 3 years of
Prednisone treatment in Surinam.
Kidney failure was diagnosed at the Nephrology Department, Free University Medical Center, Amsterdam, The Netherlands; the
cortisone treatment was interrupted and dialysis was started. At this stage, a microcytic
hypochromic anemia was observed with high reticulocyte (40%) and
ferritin (500 microg/L) levels, and
hemoglobinopathy was suspected. No abnormal bands were visible on alkaline electrophoresis and high performance liquid chromatography (HPLC). The
Hb A2 level was normal (2.7%) and the erythrocyte count was low (3.59 x 10(12)/L) with a normal
haptoglobin level (68 mg/100 mL). None of the common
alpha-thalassemia (thal) deletion defects were present. The
beta-globin gene sequence was normal but the alpha2-globin gene sequence revealed an ATG-->ATA transition at
codon 32, changing the
methionine into an
isoleucine residue. The mutation, called
Hb Amsterdam, was observed in the mother of the proband, who was also heterozygous for the--alpha3.7-thal deletion and affected by a moderate microcytic
hypochromic anemia. Both
Hb Amsterdam and the--alpha(-3.7) allele were found in association with a new polymorphism, IVS-I-39 (C-->T), previously observed in our laboratory in seven patients of African origin, on both the alpha1 and alpha2 genes. In addition,
Hb Amsterdam was also associated with the common African alpha2 polymorphism (G-->CTCGGCCC at position 7238 and T-->G at position 7174).
Hb Amsterdam is the first mutation ever described at
codon alpha32, a position involved in alpha1/beta1 interaction. The possibility of a contribution of this mutation to the nephropatic state of the proband is discussed.