A new cause of haemolytic anaemia in the newborn. A description of an unstable fetal haemoglobin: F Poole, alpha2-G-gamma2 130 trptophan yeilds glycine.

Abstract

In a newborn twin with haemolytic anaemia an unstable fetal haemoglobin was found to be the cause. The anaemia improved spontaneously with the disappearance of the fetal haemoglobin. The new Hb F (alpha2gamma2) variant was shown to have a glycine at position 130 of the 146 residues of the gamma chain. This portion is inside the globin molecule and in all known normal globins it is occupied by a residue with a bulky hydrophobic side chain. Its replacement by glycine which has no side chain would be expected to cause instability. The human gamma-chains may either have a glycine or an alanine at position 136. Evidence is brought forward to suggest that in the abnormal chain position 136 is occupied by glycine.

An unstable haemoglobin, Hb Tacoma beta30 (B12) arg leads to ser, detected at birth by the demonstration of red cell inclusions.

“…This difficulty is magnified when the variant haemoglobin is unstable. Many labile variants have the same electrophoretic mobility as Hb A (White and Dacie, 1971), and Hb F is itself inherently unstable and may therefore interfere with instability tests (Carrell, 1975;Lee-Potter et al, 1975). In addition, the amount of unstable haemoglobin present in the adult carrier is often below the 40-45 % usual for stable f-chain variants (White and Dacie, 1971), so that correspondingly lower values may be expected at birth.…”

“…It is only recently, with the reporting of the first y-chain labile mutant, Hb F Poole (Lee-Potter et al, 1975), that an unstable haemoglobin has been implicated as a possible cause of haemolysis in the new-born, yet the early detection of carriers is obviously important if the susceptibility of the molecule to oxidative degradation is considered.…”

Three Novel Spectrin Variants in Jaundiced Neonates

“…Heinz bodies were prominent on supravital stain. DNA sequencing of the gamma globin genes excluded the diagnosis of hemoglobin F Pool, 10 and did not identify any other mutations.…”

Further Investigations of the <i>γ</i>-Chain in a Ghanaian Adult, Homozygous for Hereditary Persistence of Fetal Haemoglobin

“…Blood samples were obtained from infants heterozygous for Hb F Texas I [6], Hb F Port Royal [71, Hb F Poole [8] and adult homozygous for HPFH [1], homoz ygous Hb S with raised Hb F, and a patient with raised Hb F due to leukaemia. The Hb F fractions were either separated from haemolysates by DEAE Sephadex chro matography [9] prior to removing the haem [10] or the total haemolysate was used for the determination o f glycine/alanine ratio at position /136.…”