Unusual Muscle Pathology in Mcleod Syndrome

J Neurol Neurosurg Psychiatry 2000;69:655–657 655 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.69.5.655 on 1 November 2000. Downloaded from SHORT REPORT Unusual muscle pathology in McLeod syndrome M H Barnett, F Yang, H Iland, J D Pollard Abstract antigens, and the absence of the Kx antigen.4 Muscle pathology in McLeod syndrome is The responsible gene, XK, is located on chro- usually mild; patchy necrotic or regener- mosome Xp21, between the loci of chronic ating fibres, occasional internal nuclei, granulomatous disease and Duchenne muscu- and the absence of an inflammatory cell lar dystrophy5; rarely, these disorders may infiltrate are the usual findings. We report occur concurrently.67The muscle biopsy find- on a 29 year old man presenting with ings are variable, but usually subtle.2 We report chronic fatiguability and excessive sweat- on a patient with the McLeod phenotype and ing in whom an open quadriceps muscle striking atypical mononuclear cell infiltrates on biopsy demonstrated grouped necrotic muscle biopsy. fibres accompanied by striking patchy mononuclear cell infiltrates. The diagno- Case report sis of McLeod syndrome was made on the A 29 year old carpenter presented witha5year basis of red blood cell acanthocytosis, history of persistent fatigue and excessive raised serum creatine kinase, and weak sweating on minimal exertion, initially attrib- expression of Kell blood group antigens. uted to a febrile illness diagnosed as infectious The quadriceps muscle infiltrate con- mononucleosis. There were no classic night sisted principally of histologically typical sweats or weight loss, nor any myalgias or defi- copyright. macrophages. These cells had prominent nite weakness. His symptoms were exacerbated nucleoli, displayed numerous mitoses, by a diarrhoeal illness while in Egypt 18 and were strongly CD68+. A small popula- months after onset, at which point he sought tion of typical CD3+, CD43+ lymphocytes medical attention. Creatine kinase (CK) con- was also present. In addition, a small centrations at the time were increased to population of large atypical CD3+ cells 2000–3000 U/l, and a subsequent needle EMG was noted. Immunoperoxidase stains for was consistent with a patchy myopathic proc- CD20, CD30, CD79a, and CD56 were ess. Persistently abnormal CK concentrations negative. Immunocytochemical studies led to an open muscle biopsy of the right quad- for the common muscular dystrophies riceps, which was reported as consistent with a were normal. The muscle biopsy findings necrotising myopathy. Patchy cellular infil- highlight a potential for confusion of this trates, not typical of polymyositis, were noted at http://jnnp.bmj.com/ condition with idiopathic polymyositis. the time. The patient was nevertheless immu- Institute of Clinical The expanding range of muscle pathology nosuppressed with high dose prednisolone and Neurosciences, Royal subsequently azathioprine and oral cyclophos- Prince Alfred reported in McLeod syndrome, to which Hospital, this case adds, may reflect variable in- phamide without appreciable benefit. He was Camperdown, NSW, volvement of the XK gene on chromosome referred to our institution for review. Australia Xp21, or of the adjacent loci of Duchenne There was no known family history of M H Barnett muscular dystrophy and chronic granulo- neuromuscular disease. General examination F Yang was unremarkable, and specifically there was on September 26, 2021 by guest. Protected J D Pollard matous disease. (J Neurol Neurosurg Psychiatry 2000;69:655–657) no rash, synovitis, lymphadenopathy, or Kanematsu hepatosplenomegaly. There was no muscle Laboratories Keywords: McLeod syndrome; myopathy; muscle bi- tenderness, and no focal neurological findings. H Iland opsy The reflexes were present and symmetric, and there were no sensory abnormalities. Department of Biochemical screening disclosed a raised CK Medicine, University McLeod syndrome is one of several neuro- of 790 U/l (0–250 U/l), and a mildly raised of Sydney, NSW 2006, muscular disorders associated with serum bilirubin and LDH. Serum haptoglob- Australia 1 F Yang acanthocytosis. It is characterised by myopa- ins were depressed. The reticulocyte count was J D Pollard thy, choreiform movements, raised creatine not increased and there was no myoglobin in kinase, and persistent low grade haemolysis. the urine. A mild thrombocytopenia of Correspondence to: Peripheral neuropathy, cardiomyopathy, and 137x109/l platelets was present on an otherwise Professor J D Pollard [email protected] atrophy of the caudate nuclei on MRI are less unremarkable full blood count. The blood film, often seen.1–3 The diagnosis is suggested by the however, disclosed marked acanthocytosis Received 6 March 2000 and presence of acanthocytosis in the appropriate (about 35% of erythrocytes) and occasional in revised form 26 June 2000 clinical setting, and confirmed by the de- spherocytes. Serum ANA, ENA, RF, ANCA, Accepted 19 July 2000 pressed expression of the Kell blood group HIV, and quantitative immunoglobulins were www.jnnp.com 656 Barnett, Yang, Iland, et al J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.69.5.655 on 1 November 2000. Downloaded from have, to our knowledge, not been previously reported in McLeod syndrome. They highlight a potential for confusion of this condition with idiopathic polymyositis, in which patchy inflammatory infiltrates consist predominantly of CD8+ T cells. Although macrophages may be seen in association with degenerating muscle fibres various myopathies including the au- toimmune myositides, the conspicuous infiltrates and paucity of associated lymphocytes are unusual. Our patient received potentially harmful therapy with prednisone, azathioprine, and oral cyclophosphamide before the diagnosis became apparent. Recognition of the wide phenotypic range of McLeod syndrome, both clinical and histopathological, could help avert such a scenario. Muscle biopsy in most patients exhibits myopathic changes including scattered necrotic and regenerating fibres, internal nu- Left quadriceps muscle biopsy; haematoxylin and eosin. Necrotic fibres with histiocytic cell clei, and the absence of inflammatory cell infiltrate. Bar=1 µm. infiltration.28 Kawakami et al reported more advanced myopathic changes reminiscent of normal. There was serological evidence of pre- the muscular dystrophies in a patient with vious exposure to EBV. The serum lipid profile McLeod syndrome; however, again no inflam- was normal. A CT of chest, pelvis, and matory cell infiltrates were seen.9 Similarly the abdomen was normal other than mild enlarge- clinical symptoms range from asymptomatic to ment of the right lobe of the thyroid gland. overt weakness, with or without associated car- Ultrasonography of the neck demonstrated a diomyopathy, choreoathetosis, or peripheral small thyroid nodule, and subsequent fine nee- neuropathy.12Atrophy of the caudate nuclei on dle aspiration biopsy showed a benign follicular MRI of the brain has been reported, but was pattern. not evident in our patient. The underlying genetic heterogeneity of MUSCLE PATHOLOGY McLeod syndrome may account for the copyright. The right quadriceps muscle biopsy was described clinical and pathological reviewed. Many necrotic fibres undergoing diversity.51011The proximity of the responsible phagocytosis were evident. Grouped necrotic gene, XK, to the loci of CGD and DMD fibres were accompanied in several sections by accounts for the rare concurrence of these dis- striking mononuclear cell infiltrates (figure). eases, presumably due to large deletions of the The vast majority of these cells were histologi- X chromosome.67 Preliminary analysis of our cally typical of macrophages, had prominent patient’s XK gene by direct sequencing has nucleoli, displayed numerous mitoses, and established the presence of a novel missense were strongly CD68+. A small population of point mutation.12 typical CD3+, CD43+ lymphocytes was Examination of the peripheral blood film in present, consisting of about equal numbers of this patient prompted further investigation and CD8+ and CD4+ T cells. A further small led to the diagnosis of McLeod syndrome. http://jnnp.bmj.com/ population of histologically distinct and unusu- Reviewing red cell morphology for the pres- ally large CD3+ cells was noted. Immunoper- ence of acanthocytosis is a sensitive and oxidase stains for CD20, CD30, CD79a, and inexpensive screening test for the McLeod syn- CD 56 were negative. Immunocytochemical drome, and should be performed for any studies showed normal dystrophin expression. patient who carries a diagnosis of inflammatory A further open biopsy of the left deltoid muscle muscle disease with either atypical biopsy find- performed 12 months after cessation of immu- ings or poor response to immunosuppressive nosuppressive therapy showed variation in fibre therapy. on September 26, 2021 by guest. Protected size and scattered necrotic fibres only. KELL ANTIGEN EXPRESSION We thank Mrs M Nelson for performing flow cytometry for Kell antigen expression. Kell antigen expression was evaluated by flow cytometry with polyclonal anti-Kell antibodies. Expression of both members of the 1 Hardie RJ, Pullon HWH, Harding AE, et al. Neuroacan- thocytosis: a clinical, haematological and pathological antithetical pair Kell (K1) and Cellano (K2) study of 19 cases. Brain 1991;114:13–49. was reduced, consistent with the McLeod syn- 2 Swash M, Schwartz MS, Carter ND, et al. Benign x linked myopathy with acanthocytes (McLeod syndrome). Brain drome. Anti-Kx antibodies for definitive dem-

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