Co-existence of hereditary spherocytosis and a new red cell pyruvate kinase variant: PK mallorca.
OBJECTIVE
A partial red blood cell (RBC) pyruvate-kinase (PK-R) deficiency was found in a patient with concomitant hereditary spherocytosis (HS) and chronic hemolytic anemia. Clinical, biological and molecular studies were performed in the patient, his parents and a brother, in order to characterize the specific PK-R gene mutation and the inheritance mechanism of the transmission of both red cell defects in this particular family.


METHODS
Conventional biological studies were used to identify the PK-LR gene mutation responsible for hereditary transmission of PK-R deficiency and HS. The family study was completed with genotypic and RBC membrane protein analyses in the patient and his family.


RESULTS
Molecular study of the PK deficiency was performed in all the family members and demonstrated a heterozygous condition for the 1516 G->A (506Val->Ile) mutation at the PK-LR gene in both the patient and his mother. Since this mutation has not been reported previously, it is provisionally named PK "Mallorca". The study of RBC membrane proteins demonstrated the existence of partial band 3 and protein 4.2 deficiencies in the propositus and his father but not in the mother and brother, who were also studied. These results support the dominant mode of inheritance of HS and PK-LR gene in this family.


CONCLUSIONS
HS and PK deficiency are not exceptional in Spain. The co-existence of both RBC defects in the same patient, however, is very rare; only a few cases have been described to date. Our findings suggest that performing an elementary RBC enzyme survey in all patients with HS would help to determine the real frequency of this apparently rare association.
Zarza
R
R
Red Cell Pathology Unit, Institute of Hematology and Oncology, IDIBAPS, Hospital Clínic i Provincial of Barcelona, Spain.
Moscardó
M
M
Alvarez
R
R
García
J
J
Morey
M
M
Pujades
A
A
Vives-Corrons
J L
JL
D019943:Amino Acid Substitution; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D003598:Cytoskeletal Proteins; D004910:Erythrocyte Membrane / Q000737:chemistry; D004912:Erythrocytes / Q000201:enzymology*; D005091:Exons; D005192:Family Health; D014644:Genetic Variation; D006403:Hematologic Tests; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011770:Pyruvate Kinase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013103:Spherocytosis, Hereditary / Q000235:genetics*
D001457:Anion Exchange Protein 1, Erythrocyte; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C044791:erythrocyte membrane band 4.2 protein; C412008:pyruvate kinase Mallorca; D011770:Pyruvate Kinase