McLeod syndrome 5683212 221659594 2008-06-25T14:29:55Z 69.255.73.99 {{dablink|This article is about the genetic disease of the blood, not [[MacLeod's syndrome]] (the lung disease).}} '''McLeod syndrome''' (or ''McLeod phenomenon'') is a [[genetic disorder]] that may affect the [[blood]], [[brain]], [[peripheral nerves]], [[muscle]] and [[heart]]. It is caused by a variety of recessively-inherited mutations in the XK gene on the [[X chromosome]]. The gene is responsible for producing a specific protein ([[Kell antigen]]) on the [[red blood cell]] surface. ==Clinical Features== Patients usually begin to notice symptoms in their 50s and the course is usually slowly progressive. Common features include [[peripheral neuropathy]], [[cardiomyopathy]] and [[hemolytic anemia]]. Other features include limb [[chorea (disease)|chorea]], facial [[tics]], other oral movements (lip and tongue biting), [[seizures]], a late-onset [[dementia]] and behavioral changes. ==Laboratory Features== McLeod syndrome is one of three disorders in which acanthocytes may be found on the peripheral blood smear. Blood evaluation may show signs of hemolytic anemia. Elevated creatine kinase can be seen with myopathy in McLeod syndrome. ==Radiologic and Pathologic Features== MRI shows increased T2 signal in the lateral putamen with caudate atrophy and secondary lateral ventricular dilation. Necropsy shows loss of neurons and gliosis in the caudate and globus pallidum. Similar changes may also be seen in the thalamus, substantia nigra and putamen. The cerebellum and cerebral cortex are generally spared. ==History== McLeod syndrome was discovered in [[1961]] and, as with the [[Kell antigen system]], was named after the first patient in which it was found: a [[Harvard]] dental student Hugh McLeod, whose [[red blood cell]]s were observed to be [[hemolysis|hemolysed]] during [[blood donation]],<ref>Allen FH Jr, Krabbe SM, Corcoran PA. ''A new phenotype (McLeod) in the Kell blood-group system.'' Vox Sang. 1961 Sep;6:555-60. PMID 13477267</ref> and his red cells were found to be [[acanthocyte|acanthocytic]] (spiky) under the microscope. ==Genetics== The McLeod phenotype is a [[Recessive gene|recessive]] [[mutation]] of the [[Kell antigen system|Kell blood group system]]. The McLeod [[gene]] encodes the [[XK (protein)|XK protein]], which is located on the [[X chromosome]], and has the structural characteristics of a [[membrane transport]] [[protein]] but an unknown function. Absence of the XK protein is an [[Sex linkage|X-linked disease]]. <ref>Ho MF, Monaco AP, Blonden LA, van Ommen GJ, Affara NA, Ferguson-Smith MA, Lehrach H. ''Fine mapping of the McLeod locus (XK) to a 150-380-kb region in Xp21.'' Am J Hum Genet. 1992 Feb;50(2):317-30. PMID 1734714</ref> Mutational variants result in McLeod syndrome either with or without [[neuroacanthocytosis]]: the gene on the X chromosome for McLeod syndrome is physically close to the gene for [[chronic granulomatous disease]]. As a result, individuals with one disease may have both. <ref>Marsh WL, Oyen R, Nichols ME, Allen FH Jr. ''Chronic granulomatous disease and the Kell blood groups.'' Br J Haematol. 1975 Feb;29(2):247-62. PMID 1191546</ref> ==Epidemiology and disease associations== McLeod syndrome is present in 0.5 to 1 per 100,000 of the population. McLeod males have variable [[acanthocyte|acanthocytosis]] due to a defect in the inner leaflet bilayer of the [[red blood cell]], as well as mild [[hemolysis]]. McLeod females have only occasional acanthocytes and very mild [[hemolysis]]; the lesser severity is thought to be due to [[X chromosome]] inactivation via the [[Lyon effect]]. Some individuals with McLeod phenotype develop [[myopathy]], [[neuropathy]] or psychiatric symptoms, producing a syndrome that may mimic [[chorea (disease)|chorea]].<ref>Danek A, Rubio JP, Rampoldi L, Ho M, Dobson-Stone C, Tison F, Symmans WA, Oechsner M, Kalckreuth W, Watt JM, Corbett AJ, Hamdalla HH, Marshall AG, Sutton I, Dotti MT, Malandrini A, Walker RH, Daniels G, Monaco AP. ''McLeod neuroacanthocytosis: genotype and phenotype.'' Ann Neurol. 2001 Dec;50(6):755-64. PMID 11761473</ref><ref>Malandrini A, Fabrizi GM, Truschi F, Di Pietro G, Moschini F, Bartalucci P, Berti G, Salvadori C, Bucalossi A, Guazzi G. ''Atypical McLeod syndrome manifested as X-linked chorea-acanthocytosis, neuromyopathy and dilated cardiomyopathy: report of a family.'' J Neurol Sci. 1994 Jun;124(1):89-94. PMID 7931427</ref> McLeod syndrome can cause an increase in the enzymes [[creatine kinase]] (CK) and [[lactate dehydrogenase]] (LDH) found in routine blood screening. <ref>Oechsner M, G. Winkler G, A. Danek A, ''McLeod neuroacanthocytosis: An underdiagnosed syndrome?'' International communication forum in human molecular genetics Sep 6 1995 [http://hum-molgen.org/documents/abstracts/0050.html]</ref> <ref>[http://www.neuro.wustl.edu/neuromuscular/msys/cardiac.html#mcl Neuromuscular Disease Center] Dilated cardiomyopathies ± Myopathy</ref> ==Treatment== There is no cure for McLeod syndrome, but treatment is supportive depending on symptoms. Medication may assist management of epilepsy, cardiac and psychiatric features, although patients may respond poorly to treatment for chorea. ==External links== *{{OMIM|314850}} OMIM entry on Kell blood group precursor, XK ==Notes== 8. Bradley et al. Neurology in Clinical Practice. The Neurological Disorders. 4th edition. Volume II. <references/> [[Category:Genetic disorders]] [[Category:Hematology]] [[Category:Syndromes]] [[fr:syndrome de McLeod]]