Chorea‐acanthocytosis: A report of three new families and implications for genetic counselling

Vance, Jefferey; Pericak‐Vance, Margaret A.; Bowman, Michael H; Payne, Cynthia S.; Fredane, Lewis; Siddique, Teepu; Roses, Allen D.; Massey, E. Wayne

doi:10.1002/ajmg.1320280219

Cited by 31 publications

(13 citation statements)

References 18 publications

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“…Chorea‐acanthocytosis is characterized clinically by variable expression between families3, 14 and even within the same family 15. Our three families confirm this observation.…”

Section: Discussionsupporting

confidence: 85%

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Chorea‐acanthocytosis: Clinical and genetic findings in three families from the Arabian peninsula

et al. 2002

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Chorea-acanthocytosis is a rare autosomal recessive disorder. Its characteristics are orofacial dyskinesia, hyporeflexia, seizures, aberrant behavior, atrophy of the caudate and putamen, and acanthocytes in the blood with a normal level of lipoproteins. We describe three families with chorea-acanthocytosis. The inheritance pattern was recessive and the average age at onset was 27 years (range, 18-35 years). The presenting symptoms were seizures, aberrant behaviour, chorea, tics, and/or abnormal gait. Phase-contrast and electron microscopy examinations of blood showed 10 to 40% acanthocytes. The lipid profile was normal except that, in one family, no prebetalipoprotein bands corresponding to the fraction of very low-density lipoprotein were seen in high-resolution lipoprotein electrophoresis. Magnetic resonance imaging of the brain showed marked atrophy in the caudate and putamen; 18-fluorodeoxyglucose positron emission tomography scan showed hypometabolism in the striatum. In all three families, the disease was linked to a 6-cM region of chromosome 9q21 flanked by the recombinant markers GATA 89a11 and D9S1843. This finding strongly suggests the involvement of a single locus for this syndrome. Three different homozygous mutations of this gene have been identified. Although the clinical presentation was variable, the genetic studies on these three Saudi Arabian families with chorea-acanthocytosis provide strong evidence for a genetic locus for chorea-acanthocytosis at chromosome 9q21.

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“…Chorea‐acanthocytosis is characterized clinically by variable expression between families3, 14 and even within the same family 15. Our three families confirm this observation.…”

Section: Discussionsupporting

confidence: 85%

“…Markedly elevated CK (>10 times normal) was surprisingly seen in 4 of 8 patients. In previous reports, such elevated values were noted in only 1 of 4 patients15 and 2 of 10 patients 16. In our patients, this enzyme originated in the muscles.…”

Section: Discussionsupporting

confidence: 52%

Chorea‐acanthocytosis: Clinical and genetic findings in three families from the Arabian peninsula

et al. 2002

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“…To increase sensitivity, our test procedure uses the phenomenon that acanthocytic RBC are more sensitive to echinocytic stress via isotonic dilution of the blood compared with normal RBC,in particular in unfixed wet blood preparations [4]. The patient cohort with MDs fulfilling specific clinical criteria enrolled during the prospective study period contained the usual distribution of MDs and comprised all major differential diagnoses of neuroacanthocytosis syndromes [1,2,5,10,11,13], but represents the selection of patients at highly specialized movement disorder clinics. However, our results should be representative for neurological outpatient clinics and therefore applicable to the routine daily use in such institutions.…”

Section: Discussionmentioning

confidence: 99%

Testing for acanthocytosis

2005

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The presence of acanthocytosis in peripheral blood smears remains the hallmark of the clinical diagnosis of most neuroacanthocytosis syndromes, such as chorea-acanthocytosis (ChAc) and McLeod syndrome. Genetic analyses and/or specific laboratory tests are available only for a minority of these disorders. Testing for acanthocytosis is hampered by the lack of data on normal amounts of acanthocytes assessed by a standardized method. We report a prospective reader-blinded study designed to establish control values for abnormally shaped erythrocytes in healthy volunteers and patients with movement disorders (MDs) using light microscopic assessment of erythrocyte morphology in standard EDTA and isotonically diluted blood samples. We investigated a total of 100 patients fulfilling clinical criteria of specific MDs, 31 patients with MDs not matching any clinical criteria, and 37 healthy controls. In patients with diagnosed MDs and healthy controls, acanthocytes in dry blood smears were significantly more frequent following isotonic dilution compared with standard EDTA blood. In unfixed wet blood preparations of both EDTA blood and isotonically diluted blood, acanthocyte levels were significantly higher than in standard dry blood smear preparations. There were no statistical differences of acanthocyte levels in all test conditions between diagnosed MDs and healthy volunteers. There was no significant correlation of acanthocyte levels in all blood samples and preparations with age, sex or diagnosis. Thus, normal values were defined as the 99th percentile of combined results of the two groups of volunteers. Diluted blood combined with wet blood preparation showed high specificity (0.98) and the highest sensitivity of all test procedures (all genetically confirmed ChAc patients were detected). The reported method is cheap, readily available, and provides high specificity and sensitivity in respect to clinically relevant acanthocytosis. The use of isotonically diluted blood samples combined with unfixed wet blood preparation with a normal range of <6.3% of total erythrocytes is recommended to search for significant acanthocytosis in movement disorders.

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“…4 Their movement disorder appears earlier than in McLeod syndrome, and habitual biting of tongue and lips is common. 17,[23][24][25][26][27] The nigrostriatal system seems regularly affected. 8,28,29 Parkinsonism is not uncommon in choreoacanthocytosis but has not yet been observed in McLeod syndrome.…”

Section: Discussionmentioning

confidence: 99%

The chorea of McLeod syndrome

et al. 2001

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Among the movement disorders associated with acanthocytosis, McLeod syndrome (McKusick 314850) is the one that is best characterized on the molecular level. Its defining feature is low reactivity of Kell erythrocyte antigens. This is due to absence of membrane protein KX that forms a complex with the Kell protein. KX is coded for by the XK gene on the X-chromosome. We present six males (aged 29 to 60 years), with proven XK mutations, to discuss the chorea associated with McLeod syndrome. The movement disorder commonly develops in the fifth decade and is progressive. It affects the limbs, the trunk and the face. In addition to facial grimacing, involuntary vocalization can be present. In early stages there may only be some restlessness or slight involuntary distal movements of ankles and fingers. Lip-biting and facial tics seem more common in autosomal recessive choreoacanthocytosis linked to chromosome 9. This, together with the absence of dysphagia in McLeod syndrome, may help in differential diagnosis. Recent findings suggest a role for the endothelin system of the striatum in the pathogenesis of McLeod syndrome.

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Chorea‐acanthocytosis: A report of three new families and implications for genetic counselling

Cited by 31 publications

References 18 publications

Chorea‐acanthocytosis: Clinical and genetic findings in three families from the Arabian peninsula

Chorea‐acanthocytosis: Clinical and genetic findings in three families from the Arabian peninsula

Testing for acanthocytosis

The chorea of McLeod syndrome

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