Erythrocyte bisphosphoglycerate mutase (BPGM) deficiency is a rare disease associated with a decrease in 2,3-diphosphoglycerate concentration. A complete BPGM deficiency was described in 1978 by Rosa et al (J Clin Invest 62:907, 1978) and was shown to be associated with 30% to 50% of an inactive enzyme detectable by specific antibodies and resulting from an 89 Arg-->Cys substitution. The propositus' three sisters exhibited the same phenotype, while his two children had an intermediate phenotype. Samples from the family were examined using polymerase chain reaction and allele-specific oligonucleotide hybridization and sequencing techniques. Amplification of erythrocyte total RNA from the propositus' sister around the 89 mutation indicated the presence of two forms of messenger RNAs, a major form with the 89 Arg-->Cys mutation and a minor form with a normal sequence. Sequence studies of the propositus' DNA samples indicated heterozygosity at locus 89 and another heterozygosity with the deletion of nucleotide C 205 or C 206. Therefore, the total BPGM deficiency results from a genetic compound with one allele coding for an inactive enzyme (mutation BPGM Creteil I) and the other bearing a frameshift mutation (mutation BPGM Creteil II). Examination of the propositus' two children indicated that they both inherited the BPGM Creteil I mutation.

Based on the results of this study, intensive multimodality therapy appears feasible and effective in this group of patients.

Phosphoglycerate kinase (PGK) deficiency is generally associated with chronic hemolytic anemia, although it can be accompanied by either mental retardation or muscular disease. Genomic DNAs of two PGK- deficient patients previously described in France were sequenced directly after polymerase chain reaction amplification. The PGK Creteil variant arises from a G-->A nucleotide interchange at position 1022 in cDNA (exon 9), resulting in amino acid substitution 314 Asp-->Asn in the C-terminal domain, which contains the nucleotide binding site. It is associated with rhabdomyolysis crises but not with hemolysis or mental retardation. In the other case, which is associated with chronic hemolytic anemia and mental retardation (PGK Amiens), an A-->T nucleotide interchange was found at position 571 in cDNA (exon 5); this leads to amino acid substitution 163 Asp-->Val in the N-terminal domain, which contains the catalytic site for phosphoglycerate binding. These results corroborate the kinetic data observed. In the two cases, the mutations are distinct from others previously reported and no significant relationship could be observed between the location of the amino acid substitution and its clinical consequences.

A Guinean woman, hetererozygous for haemoglobin (Hb) S, was studied because of episodes of marked anaemia, repeated typical metaphyseal painful crises and haemosiderosis. Her sickling syndrome resulted from the association of Hb S trait with a severe pyruvate kinase deficiency leading to a 2,3‐DPG concentration of twice normal levels. Sequence of the PK‐R gene revealed an undescribed mutation in the homozygous or hemizygous state within exon 5 (nucleotide 2670 C → A), leading to the interchange of Ser 130 into Tyr (PK Conakry). In addition, the patient carried a new haemoglobin variant, Hb Conakry [α80(F1) Leu  → Val], which seemed to have a mild effect. The high intraerythrocytic 2,3‐DPG concentration induced by the PK deficiency resulted in a decreased oxygen affinity which favoured sickling to a level almost similar to that of Hb S/C compound heterozygous patients. This was confirmed by oxygen binding measurements of Hb A/Hb S erythrocytes in which 2,3‐DPG content was modified in vitro. Hysteresis between deoxy‐ and reoxygenation curves, as well as increase in the nmax value, demonstrated that the extent of HbS polymerization in the propositus was almost the same as that of RBCs from a homozygous sickle cell patient or those of an A/S heterozygous patient with an artificial in vitro increase of 2,3‐DPG concentration.

A new case of a defect in red cell pyrimidine 5'-nucleotide (P5N) activity was found in a large family from Guadeloupe in the West Indies. The propositus presented a characteristic hemolytic anemia with red cell basophilic stippling, an increased GSH level, and a shift of the peak in absorbance of nucleotide. The enzyme activity from the deficient red cells differed from that of the normal. The P5N activity of the deficient red cells was about 14% that of normal. The electrophoretic pattern of P5N activity of the deficient red cells was distinct from that of the control in terms of its Km and of the effects of pH on its maximum activity and heat stability. The significance of such differences is discussed.