McLeod syndrome was first described in a trainee dentist, after whom the condition is named. In most cases it occurs due to truncation of the XK gene, present on Xp21. As the protein occurs on red cell membrane as a heterodimer, linked to the Kell antigen, the condition can sometimes be picked up by the Blood Bank due to the absence or attenuation of the Kell blood group antigen.
Mcleod syndrome shares many features with choreo-acanthocytosis, an autosomal recessive condition caused by defects in a protein called chorein. However, the latter does not have the blood group phenotype of McLeod syndrome- i.e. reduced or absent Kell antigen and absent XK antigen (also called Kx antigen).
McLeod Syndrome can occur alone, or as part of the contiguous gene deletion syndrome affecting neighbouring genes on the short arm of X-chromosome, leading to congenital adrenal hypoplasia, Duchenne Muscular Dystrophy (DMD), X-linked Retinitis Pigmentosa, or combinations thereof.
All documented men with McLeod syndrome have a raised CK between 400-4000 IU/l. It happens even in subjects without contiguous gene deletion, and cannot therefore be attributed to DMD.
Here's where it gets interesting. Similar elevations in CK can be seen in subjects with Glycerol Kinase deficiency, which is also coded on Xp21. This has infantile, juvenile and adult forms, and most with the adult form are asymptomatic except for 2 findings- hypertriglyceridaemia and raised CK. The infantile and occasionally, the juvenile form presents with abdominal pain, non-ketotic hypoglycemia and seizures, much like the carnitine disorders presented elsewhere in this blog.
The hypertiglyceridaemia seen in subjects with glycerol kinase deficiency is actually a pseudo-phenomenon. These subjects in fact have markedly raised serum glycerol, which tests positive in assays for triglycerides. Think of this condition when you see raised CK and high triglycerides in an adult male who is otherwise well.
Nobody knows why these two disparate conditions arising from gene defects on Xp21 should have raised CK. This is currently unexplained.
Curiously, subjects with choreo-acanthocytosis due to reduction in chorein also have a raised CK. However, this is an autosomal recessive condition and therefore cannot be attributed to the X-chromosome.
Mcleod syndrome shares many features with choreo-acanthocytosis, an autosomal recessive condition caused by defects in a protein called chorein. However, the latter does not have the blood group phenotype of McLeod syndrome- i.e. reduced or absent Kell antigen and absent XK antigen (also called Kx antigen).
McLeod Syndrome can occur alone, or as part of the contiguous gene deletion syndrome affecting neighbouring genes on the short arm of X-chromosome, leading to congenital adrenal hypoplasia, Duchenne Muscular Dystrophy (DMD), X-linked Retinitis Pigmentosa, or combinations thereof.
All documented men with McLeod syndrome have a raised CK between 400-4000 IU/l. It happens even in subjects without contiguous gene deletion, and cannot therefore be attributed to DMD.
Here's where it gets interesting. Similar elevations in CK can be seen in subjects with Glycerol Kinase deficiency, which is also coded on Xp21. This has infantile, juvenile and adult forms, and most with the adult form are asymptomatic except for 2 findings- hypertriglyceridaemia and raised CK. The infantile and occasionally, the juvenile form presents with abdominal pain, non-ketotic hypoglycemia and seizures, much like the carnitine disorders presented elsewhere in this blog.
The hypertiglyceridaemia seen in subjects with glycerol kinase deficiency is actually a pseudo-phenomenon. These subjects in fact have markedly raised serum glycerol, which tests positive in assays for triglycerides. Think of this condition when you see raised CK and high triglycerides in an adult male who is otherwise well.
Nobody knows why these two disparate conditions arising from gene defects on Xp21 should have raised CK. This is currently unexplained.
Curiously, subjects with choreo-acanthocytosis due to reduction in chorein also have a raised CK. However, this is an autosomal recessive condition and therefore cannot be attributed to the X-chromosome.
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