Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis.
In a family with mild dominant spherocytosis, affected members showed partial band 3 deficiency. The index patient showed more severe clinical symptoms than his relatives, and his red blood cells displayed concomitant low pyruvate kinase activity. We investigated the contribution of partial PK deficiency to the phenotypic expression of mutant band 3 in this family. Pyruvate kinase deficiency and band 3 deficiency were characterized by DNA analysis. Results of red cell osmotic fragility testing, the results of cell deformability obtained by the Automated Rheoscope and Cell Analyzer and the results obtained by Osmotic Gradient Ektacytometry, which is a combination of these tests, were related to the red cell ATP content. Spherocytosis in this family was due to a novel heterozygous mutation in SLC4A1, the gene for band 3. Reduced PK activity of the index patient was attributed to a novel mutation in PKLR inherited from his mother, who was without clinical symptoms. Partial PK deficiency was associated with decreased red cell ATP content and markedly increased osmotic fragility. This suggests an aggravating effect of low ATP levels on the phenotypic expression of band 3 deficiency.
Laboratory of Red Blood Cell Diagnostics, Department of Blood Cell Research, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands.
Rob
R
van Zwieten
Brigitte A
BA
van Oirschot
Martijn
M
Veldthuis
Johannes G
JG
Dobbe
Geert J
GJ
Streekstra
Wouter W
WW
van Solinge
Roger E G
RE
Schutgens
Richard
R
van Wijk
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency / Q000235:genetics*; D017487:Ankyrins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009996:Osmotic Fragility; D010375:Pedigree; D010641:Phenotype; D011770:Pyruvate Kinase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015323:Pyruvate Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013103:Spherocytosis, Hereditary / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D001457:Anion Exchange Protein 1, Erythrocyte; D017487:Ankyrins; C454201:SLC4A1 protein, human; D000255:Adenosine Triphosphate; D011770:Pyruvate Kinase