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Hereditary acanthocytosis associated with the McLeod phenotype of the Kell blood group system
Insights
The McLeod blood group phenotype, typically seen in X-linked chronic granulomatous disease (CGD), was identified in individuals without CGD. This study highlights red blood cell abnormalities as a diagnostic clue for the McLeod phenotype.
Area of Science:
- Hematology
- Genetics
- Immunology
Background:
- The McLeod phenotype in the Kell blood group system is rare and often associated with X-linked chronic granulomatous disease (CGD).
- Previous reports documented the McLeod phenotype in only one non-CGD subject.
- Red blood cell abnormalities like acanthocytosis are recognized features of the McLeod phenotype.
Purpose of the Study:
- To investigate the McLeod blood group phenotype in individuals without CGD.
- To characterize the red blood cell morphology and inheritance patterns in families with the McLeod phenotype.
- To provide further evidence for the genetic basis of the McLeod phenotype.
Main Methods:
- Hematological examination of red blood cells, including morphology and osmotic fragility testing.
- Kell blood group phenotyping.
- Family studies to trace inheritance patterns and identify carriers.
Main Results:
- A 10-year-old boy and his maternal relatives presented with the McLeod phenotype without CGD.
- Affected individuals exhibited red blood cell abnormalities: acanthocytosis, anisocytosis, and altered osmotic fragility.
- Female carriers displayed red blood cell mosaicism due to X chromosome inactivation (Lyon effect).
Conclusions:
- The McLeod phenotype can occur in individuals without CGD, with red blood cell morphology serving as a diagnostic indicator.
- The McLeod phenotype is caused by an X-linked modifying gene, not a variant gene at the Kell autosomal locus.
- This study confirms X-linked inheritance and demonstrates red cell abnormalities as the initial recognition feature for a rare blood group.
Abstract:
Some boys with X-linked chronic granulomatous disease (CGD) have red cells of the rare McLeod phenotype in the Kell blood group system. Only one example of this phenotype has previously been described in a non-CGD subject. We have studied a 10-year-old boy and a maternal brother who do not have CGD and whose red cells are of the McLeod type . The boy presented as a haematological problem with red-cell abnormalities. These were acanthocytosis, anisocytosis and 'tailing' in the osmotic fragility curve, changes now known to occur with the McLeod phenotype. Subsequent studies revealed his rare blood group. A family study has established that an uncle also has acanthocytic red cells and the McLeod phenotype. In addition the boy's sister, mother and maternal grandmother all show red-cell mosaicism with double populations of McLeod acanthocytes and normal red cells of common Kell type. The gene that determines inheritance of the McLeod phenotype is X-linked and the mosaicism present in female carriers is believed to result from X chromosome inactivation by the Lyon effect. The study provides further evidence that the McLeod phenotype arises by inheritance of a variant X-linked modifying gene and not through inheritance of a variant gene at the Kell autosomal locus. It also represents the first occasion that a person of rare blood group has been recognized because of an associated anomaly in red cell morphology.