Unusual muscle pathology in McLeod syndrome

Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Journal of Neurology Neurosurgery & Psychiatry (Impact Factor: 6.81). 12/2000; 69(5):655-7. DOI: 10.1136/jnnp.69.5.655
Source: PubMed


Muscle pathology in McLeod syndrome is usually mild; patchy necrotic or regenerating fibres, occasional internal nuclei, and the absence of an inflammatory cell infiltrate are the usual findings. We report on a 29 year old man presenting with chronic fatiguability and excessive sweating in whom an open quadriceps muscle biopsy demonstrated grouped necrotic fibres accompanied by striking patchy mononuclear cell infiltrates. The diagnosis of McLeod syndrome was made on the basis of red blood cell acanthocytosis, raised serum creatine kinase, and weak expression of Kell blood group antigens. The quadriceps muscle infiltrate consisted principally of histologically typical macrophages. These cells had prominent nucleoli, displayed numerous mitoses, and were strongly CD68+. A small population of typical CD3+, CD43+ lymphocytes was also present. In addition, a small population of large atypical CD3+ cells was noted. Immunoperoxidase stains for CD20, CD30, CD79a, and CD56 were negative. Immunocytochemical studies for the common muscular dystrophies were normal. The muscle biopsy findings highlight a potential for confusion of this condition with idiopathic polymyositis. The expanding range of muscle pathology reported in McLeod syndrome, to which this case adds, may reflect variable involvement of the XK gene on chromosome Xp21, or of the adjacent loci of Duchenne muscular dystrophy and chronic granulomatous disease.


Available from: Harry J Iland
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    • "The clinical history of this case including the unusual muscle pathology has been described previously (Barnett et al, 2000). Briefly, the patient was a 29-year-old man without a family history of neuromuscular disease. "
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    ABSTRACT: A 29-year-old man with a history of elevated creatine kinase and necrotizing myopathy was reviewed. Prominent red cell acanthocytosis in association with reduced Kell antigen expression was present, findings consistent with the McLeod syndrome. Investigation of the patient's XK gene revealed a novel TGG- to-TAG transition at position 1023 in exon 3. This point mutation creates an in-frame stop codon (W314X), and predicts a truncated XK protein of 313 amino acids, compared with 444 amino acids in the normal XK protein. The mutation was not identified in the patient's mother or sister indicating that this mutation was spontaneous.
    British Journal of Haematology 12/2001; 115(2):369-72. DOI:10.1046/j.1365-2141.2001.03121.x · 4.71 Impact Factor
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    ABSTRACT: McLeo dsyndrom ei scause db ymutation so fXK ,a nX-chromosoma lgen eo funknow nfunction .Originall ydefine das apeculia rKel lbloo dgrou pvariant ,th ediseas eaffect smultipl eorgans ,includin gth enervou ssystem ,bu ti scertainly underdiagnosed .W eanalyze dth emutation san dclinica lfinding so f2 2affecte dmen ,age d2 7t o7 2years .Fifteen differen tX Kmutation swer efound ,nin eo fwhic hwer enovel ,includin gth eon eo fth eeponymou scas eMcLeod .Their commo nresul ti spredicte dabsenc eo rtruncatio no fth eX Kprotein .Al lpatient sshowe delevate dlevel so fmuscle creatin ephosphokinase ,bu tclinica lmyopath ywa sles scommon .A periphera lneuropath ywit hareflexi awa sfoun di nall bu t2 patients .Th ecentra lnervou ssyste mwa saffecte di n1 5patients ,a sobviou sfro mth eoccurrenc eo fseizures, cognitiv eimpairment ,psychopathology ,an dchoreati cmovements .Neuroimagin gemphasize dth eparticula rinvolvement o fth ebasa lganglia ,whic hwa sals odetecte di n1 asymptomati cyoun gpatient .Mos tfeature sdevelo pwit hage ,mainly afte rth efourt hdecade .Th eresemblanc eo fMcLeo dsyndrom ewit hHuntington' sdiseas ean dwit hautosoma lrecessive chorea-acanthocytosi ssuggest stha tth ecorrespondin gproteins—XK ,huntingtin ,an dchorein—migh tbelon gt oa com- mo npathway ,th edysfunctio no fwhic hcause sdegeneratio no fth ebasa lganglia. An nNeuro l2001;50:755-764 Discover yo fth eMcLeo dbloo dgrou pvarian twa sa consequenc eo fth eroutin escreenin go fHarvar dstu- dent sfo rne wantibodie si nth elat e1950s .Lik eother erythrocyt ephenotypes ,th epeculia rpatter no fweakly expresse dKel lantigen sreceive dit snam efro mth epro- positus.1 Acanthocytosi s(acanth a 5thorn) ,th eabnor- ma lshap eo fthes ere dcells ,wa snote dmuc hlater.2 Diagnosi so fth eMcLeo dphenotyp ei na bo ywith chroni canemi afro ma larg eNe wZealan dfamil yled t oth erecognitio no ffeature ssuc ha shemolysis ,hepa- tomegaly ,an dsplenomegaly3 an dprove dth eassump- tio no fX-linke dinheritance.2 "McLeo dsyndrome "was
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    ABSTRACT: The McLeod syndrome is an X-linked neuroacanthocytosis manifesting with myopathy and progressive chorea. It is caused by mutations of the XK gene encoding the XK protein, a putative membrane transport protein of yet unknown function. In erythroid tissues, XK forms a functional complex with the Kell glycoprotein. Here, we present an immunohistochemical study in skeletal muscle of normal controls and a McLeod patient with a XK gene point mutation (C977T) using affinity-purified antibodies against XK and Kell proteins. Histological examination of the affected muscle revealed the typical pattern of McLeod myopathy including type 2 fiber atrophy. In control muscles, Kell immunohistochemistry stained sarcoplasmic membranes. XK immunohistochemistry resulted in a type 2 fiber-specific intracellular staining that was most probably confined to the sarcoplasmic reticulum. In contrast, there was only a weak background signal without a specific staining pattern for XK and Kell in the McLeod muscle. Our results demonstrate that the lack of physiological XK expression correlates to the type 2 fiber atrophy in McLeod myopathy, and suggest that the XK protein represents a crucial factor for the maintenance of normal muscle structure and function. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1346–1351, 2001
    Muscle & Nerve 10/2001; 24(10):1346 - 1351. DOI:10.1002/mus.1154 · 2.28 Impact Factor
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