MCID: MCL009
MIFTS: 45

Mcleod Syndrome

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Blood diseases

Aliases & Classifications for Mcleod Syndrome

MalaCards integrated aliases for Mcleod Syndrome:

Name: Mcleod Syndrome 57 76 53 25 75 37
Mcleod Neuroacanthocytosis Syndrome 24 53 25 59 29 6
Mcleod Syndrome with or Without Chronic Granulomatous Disease 57 13
X-Linked Mcleod Syndrome 53 59
Mcleod Phenotype 57 75
Mls 59 75
Mcleod Syndrome with Chronic Granulomatous Disease 75
Neuroacanthocytosis, Mcleod Type 57
Neuroacanthocytosis Mcleod Type 75
Blood Group Deletion Syndrome 73
Syndrome, Mcleod 40
Mclds 57

Characteristics:

Orphanet epidemiological data:

59
mcleod neuroacanthocytosis syndrome
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Inheritance:
x-linked

Miscellaneous:
inter- and intrafamilial variability
mean age of onset between 30-40 years
disease duration ranged from 7-51 years
female carriers manifesting the mcleod phenotype have been reported


HPO:

32
mcleod syndrome:
Inheritance x-linked inheritance


GeneReviews:

24
Penetrance In males, the penetrance of neurologic and neuromuscular manifestations of mls is high after age 50 years, perhaps even complete. available data indicate that most males with the "mcleod blood group phenotype" will develop clinical symptoms of mcleod neuroacanthocytosis syndrome [bertelson et al 1988, hardie et al 1991, danek et al 2001a, jung et al 2001b]. in a few individuals, however, neurologic and neuromuscular symptoms may be absent or only minor even after long-term follow up [jung et al 2003, walker et al 2007a]...

Classifications:



Summaries for Mcleod Syndrome

OMIM : 57 Hematologically, McLeod syndrome is characterized by the absence of red blood cell Kx antigen, weak expression of Kell red blood cell antigens, acanthocytosis, and compensated hemolysis. Most carriers of this McLeod blood group phenotype have acanthocytosis and elevated serum creatine kinase levels and are prone to develop a severe neurologic disorder resembling Huntington disease (143100). Onset of neurologic symptoms ranges between 25 and 60 years (mean onset 30-40 years), and penetrance appears to be high. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy (summary by Jung et al., 2007). The cooccurrence of McLeod syndrome and chronic granulomatous disease (CGD; 306400) results from a contiguous gene deletion (Francke et al., 1985). (300842)

MalaCards based summary : Mcleod Syndrome, also known as mcleod neuroacanthocytosis syndrome, is related to choreoacanthocytosis and myopathy. An important gene associated with Mcleod Syndrome is XK (X-Linked Kx Blood Group). Affiliated tissues include heart, brain and skeletal muscle, and related phenotypes are depressivity and dysarthria

UniProtKB/Swiss-Prot : 75 McLeod syndrome: A multisystem disorder characterized by the absence of red blood cell Kx antigen, weak expression of Kell red blood cell antigens, acanthocytosis, and compensated hemolysis. Most carriers of this McLeod blood group phenotype have acanthocytosis and elevated serum creatine kinase levels and are prone to develop a severe neurologic disorder resembling Huntington disease. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy.

NIH Rare Diseases : 53 McLeod neuroacanthocytosis syndrome is primarily a neurological disorder that occurs almost exclusively in males. Only about 150 cases have been reported worldwide. This condition affects movement in many parts of the body. People with this condition also have abnormal star-shaped red blood cells (acanthocytosis). This condition is one of a group of disorders called neuroacanthocytoses that involve neurological problems and abnormal red blood cells. McLeod neuroacanthocytosis syndrome is inherited in an X-linked recessive fashion and is caused by mutations in the XK gene.

Genetics Home Reference : 25 McLeod neuroacanthocytosis syndrome is primarily a neurological disorder that occurs almost exclusively in boys and men. This disorder affects movement in many parts of the body. People with McLeod neuroacanthocytosis syndrome also have abnormal star-shaped red blood cells (acanthocytosis). This condition is one of a group of disorders called neuroacanthocytoses that involve neurological problems and abnormal red blood cells.

Wikipedia : 76 McLeod syndrome (or McLeod phenomenon; /məˈklaʊd/) is an X-linked recessive genetic disorder that may... more...

GeneReviews: NBK1354

Related Diseases for Mcleod Syndrome

Diseases related to Mcleod Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 63)
# Related Disease Score Top Affiliating Genes
1 choreoacanthocytosis 31.4 VPS13A XK
2 myopathy 28.5 DMD SGCA XK
3 dilated cardiomyopathy 28.5 DMD SGCA XK
4 o'sullivan-mcleod syndrome 12.1
5 mucolipidosis iii alpha/beta 11.8
6 mucolipidosis ii alpha/beta 11.8
7 linear skin defects with multiple congenital anomalies 1 11.8
8 mucolipidosis iv 11.6
9 neuraminidase deficiency 11.4
10 mohr-tranebjaerg syndrome 11.2
11 mucolipidosis iii gamma 11.2
12 mucolipidoses 11.1
13 anuria 11.1
14 renal tubular dysgenesis 11.1
15 doyne honeycomb retinal dystrophy 10.8
16 infantile recurrent chronic multifocal osteomyolitis 10.8
17 dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema 10.8
18 ascites, chylous 10.8
19 spermatogenic failure, y-linked, 2 10.8
20 complement factor i deficiency 10.8
21 microvascular complications of diabetes 3 10.8
22 aromatase deficiency 10.8
23 masp2 deficiency 10.8
24 mannose-binding lectin deficiency 10.8
25 primary pigmented nodular adrenocortical disease 10.8
26 inclusion-cell disease 10.8
27 glycoproteinosis 10.8
28 hypervitaminosis d 10.8
29 prostatitis 10.6
30 prostate cancer 10.5
31 microphthalmia 10.3
32 chronic granulomatous disease 10.1
33 melanoma 10.1
34 schizophrenia 10.1
35 cardiomyopathy, dilated, 3b 9.9 DMD SGCA
36 muscular dystrophy, limb-girdle, type 2c 9.9 DMD SGCA
37 cerebritis 9.9
38 muscular atrophy 9.9
39 neuropathy 9.9
40 muscular dystrophy 9.9
41 muscular dystrophy, congenital merosin-deficient, 1a 9.9 DMD SGCA
42 muscular dystrophy, limb-girdle, type 2f 9.9 DMD SGCA
43 muscular dystrophy, limb-girdle, type 2b 9.9 DMD SGCA
44 muscular dystrophy, becker type 9.8 DMD SGCA
45 autosomal recessive limb-girdle muscular dystrophy 9.8 DMD SGCA
46 muscle tissue disease 9.8 DMD SGCA
47 retinitis pigmentosa 9.8
48 muscular dystrophy, duchenne type 9.8
49 leber congenital amaurosis 4 9.8
50 polyglucosan body myopathy 1 with or without immunodeficiency 9.8

Graphical network of the top 20 diseases related to Mcleod Syndrome:



Diseases related to Mcleod Syndrome

Symptoms & Phenotypes for Mcleod Syndrome

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
dysarthria
choreatic movement disorder (in 30% of patients)
facial dyskinesia
seizures (in 20-40% of patients)
subcortical cognitive impairment (seen in 50% of patients with neuromuscular manifestations)

Cardiovascular Heart:
atrial fibrillation
dilated cardiomyopathy (in 60% of patients)

Neurologic Peripheral Nervous System:
absent deep tendon reflexes
sensory-motor axonal neuropathy

AbdomenSpleen:
hepatosplenomegaly (in some patients)

Immunology:
granuloma formation (in some patients)
recurrent bacterial and fungal infections (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
anxiety
personality disorder
depression
obsessive-compulsive disorder
psychiatric abnormalities (in 20% of patients)

Hematology:
acanthocytosis
absence of kx red blood cell antigen
weak expression of kell antigen
hemolysis, compensated

Abdomen Liver:
hepatosplenomegaly (in some patients)

Muscle Soft Tissue:
muscle weakness or atrophy (in 50% of patients)
myopathy, slowly progressive
rhabdomyolysis (rare)

Laboratory Abnormalities:
elevated serum creatine levels


Clinical features from OMIM:

300842

Human phenotypes related to Mcleod Syndrome:

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 depressivity 32 HP:0000716
2 dysarthria 32 HP:0001260
3 muscle weakness 32 HP:0001324
4 elevated serum creatine phosphokinase 32 HP:0003236
5 anxiety 32 HP:0000739
6 cardiomyopathy 32 HP:0001638
7 generalized seizures 32 HP:0002197
8 obsessive-compulsive behavior 32 HP:0000722
9 areflexia 32 HP:0001284
10 dilated cardiomyopathy 32 HP:0001644
11 atrial fibrillation 32 HP:0005110
12 hepatosplenomegaly 32 occasional (7.5%) HP:0001433
13 personality disorder 32 HP:0012075
14 acanthocytosis 32 obligate (100%) HP:0001927
15 rhabdomyolysis 32 occasional (7.5%) HP:0003201

MGI Mouse Phenotypes related to Mcleod Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.02 CKM DMD DRD2 SGCA XK

Drugs & Therapeutics for Mcleod Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Heart and Skeletal Muscle Problems in Neuroacanthocytosis Completed NCT00007228

Search NIH Clinical Center for Mcleod Syndrome

Genetic Tests for Mcleod Syndrome

Genetic tests related to Mcleod Syndrome:

# Genetic test Affiliating Genes
1 Mcleod Neuroacanthocytosis Syndrome 29 XK

Anatomical Context for Mcleod Syndrome

MalaCards organs/tissues related to Mcleod Syndrome:

41
Heart, Brain, Skeletal Muscle, Lung

Publications for Mcleod Syndrome

Articles related to Mcleod Syndrome:

(show top 50) (show all 71)
# Title Authors Year
1
McLeod syndrome is a new cause of axial muscle weakness. ( 29381810 )
2018
2
Stepwise partitioning of Xp21: a profiling method for XK deletions causative of the McLeod syndrome. ( 28555782 )
2017
3
Neurodegeneration in the elderly - When the blood type matters: An overview of the McLeod syndrome with focus on hematological features. ( 25934153 )
2015
4
Giant Axon Formation in Mice Lacking Kell, XK, or Kell and XK: Animal Models of McLeod Neuroacanthocytosis Syndrome. ( 24405768 )
2014
5
The first report of a Chinese family with McLeod syndrome. ( 24895410 )
2014
6
O'Sullivan-McLeod syndrome: clinical features, neuroradiology and nosology. ( 25488537 )
2014
7
A novel XK gene mutation in a Taiwanese family with McLeod syndrome. ( 24635891 )
2014
8
Novel single base-pair deletion in exon 1 of XK gene leading to McLeod syndrome with chorea, muscle wasting, peripheral neuropathy, acanthocytosis and haemolysis. ( 24529944 )
2014
9
Henry VIII, McLeod syndrome and Jacquetta's curse. ( 24350322 )
2013
10
The first case report of McLeod syndrome in a Chinese patient. ( 23943810 )
2013
11
The chorea of McLeod syndrome: progression to hypokinesia. ( 23192927 )
2012
12
Feeding dystonia in McLeod syndrome. ( 21714011 )
2011
13
Head drops are also observed in McLeod syndrome. ( 21469202 )
2011
14
McLeod Syndrome: Report of an Indian family with phenotypic heterogeneity. ( 21808490 )
2011
15
McLeod syndrome and acanthocytosis. ( 21808488 )
2011
16
Mcleod syndrome: Report of an Indian family with phenotypic heterogeneity. ( 21655208 )
2011
17
Evolution of striatal degeneration in McLeod syndrome. ( 19968700 )
2010
18
Identification and characterization of a novel XK splice site mutation in a patient with McLeod syndrome. ( 19040496 )
2009
19
Cardiac and neurologic involvement in McLeod syndrome. ( 18657329 )
2009
20
Electroconvulsive therapy in neuroacanthocytosis or McLeod syndrome. ( 18997633 )
2009
21
Cardiac abnormalities in McLeod syndrome. ( 18045706 )
2009
22
The McLeod syndrome without acanthocytes. ( 17870653 )
2008
23
Phenotypic variation among brothers with the McLeod neuroacanthocytosis syndrome. ( 17133513 )
2007
24
McLeod syndrome: a neurohaematological disorder. ( 17683354 )
2007
25
Phenotypic variability of a distinct deletion in McLeod syndrome. ( 17469188 )
2007
26
McLeod phenotype without the McLeod syndrome. ( 17302777 )
2007
27
Slowly progressive distal muscular atrophy of the bilateral upper limbs (O'Sullivan-McLeod syndrome) partially alleviated by intravenous immunoglobulin therapy. ( 17443046 )
2007
28
Bronchial adenoid cystic carcinoma presenting as unilateral hyperlucent lung (Swyer-James-McLeod syndrome). ( 18157603 )
2007
29
[McLeod syndrome: Multisystem involvement associated with neuroacanthocytosis linked to X chromosome. report of two related cases]. ( 17277857 )
2006
30
Cerebral metabolic alterations in McLeod syndrome. ( 16914926 )
2006
31
McLeod syndrome: life-long neuropsychiatric disorder due to a novel mutation of the XK gene. ( 16314760 )
2005
32
A family with McLeod syndrome and calpainopathy with clinically overlapping diseases. ( 16344536 )
2005
33
Schizophrenia as a manifestation of X-linked Mcleod-Neuroacanthocytosis syndrome. ( 15163264 )
2004
34
An unusual phenotype of McLeod syndrome with late onset axonal neuropathy. ( 14638894 )
2003
35
McLeod syndrome resulting from a novel XK mutation. ( 12899725 )
2003
36
The McLeod syndrome: an example of the value of integrating clinical and molecular studies. ( 11961231 )
2002
37
[Progress in molecular chorea diagnosis. McLeod syndrome and chorea acanthocytosis]. ( 12243006 )
2002
38
The chorea of McLeod syndrome. ( 11746618 )
2001
39
McLeod syndrome: a novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings. ( 11261514 )
2001
40
A spontaneous novel XK gene mutation in a patient with McLeod syndrome. ( 11703337 )
2001
41
A novel mutation of the McLeod syndrome gene in a Japanese family. ( 10930599 )
2000
42
Muscle CT scan findings in McLeod syndrome and chorea-acanthocytosis. ( 10883007 )
2000
43
McLeod syndrome (a variant of neuroacanthocytosis). ( 11229129 )
2000
44
McLeod syndrome and neuroacanthocytosis with a novel mutation in the XK gene. ( 11104227 )
2000
45
Slowly progressive spinal muscular atrophy of the hands (O'Sullivan-McLeod syndrome): clinical and magnetic resonance imaging presentation. ( 11041339 )
2000
46
Unusual muscle pathology in McLeod syndrome. ( 11032622 )
2000
47
Kell, Kx and the McLeod syndrome. ( 10895256 )
1999
48
Ultrastructural changes of erythrocyte membrane skeletons in chorea-acanthocytosis and McLeod syndrome revealed by the quick-freezing and deep-etching method. ( 10085435 )
1999
49
A case of McLeod syndrome with unusually severe myopathy. ( 10465497 )
1999
50
A novel frameshift mutation in the McLeod syndrome gene in a Japanese family. ( 10426139 )
1999

Variations for Mcleod Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Mcleod Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 XK p.Arg222Gly VAR_013817
2 XK p.Cys294Arg VAR_013818 rs28933690
3 XK p.Glu327Lys VAR_023581

ClinVar genetic disease variations for Mcleod Syndrome:

6
(show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 XK XK, IVS2DS, G-A, +1 single nucleotide variant Pathogenic
2 XK XK, IVS2AS, G-A, -1 single nucleotide variant Pathogenic
3 XK XK, 1-BP DEL deletion Pathogenic
4 XK XK, 1-BP DEL, 1095T deletion Pathogenic
5 XK NM_021083.3(XK): c.880T> C (p.Cys294Arg) single nucleotide variant Pathogenic rs28933690 GRCh37 Chromosome X, 37587260: 37587260
6 XK NM_021083.3(XK): c.880T> C (p.Cys294Arg) single nucleotide variant Pathogenic rs28933690 GRCh38 Chromosome X, 37728007: 37728007
7 XK XK, 13-BP DEL deletion Pathogenic
8 XK NM_021083.3(XK): c.941G> A (p.Trp314Ter) single nucleotide variant Pathogenic rs104894953 GRCh37 Chromosome X, 37587321: 37587321
9 XK NM_021083.3(XK): c.941G> A (p.Trp314Ter) single nucleotide variant Pathogenic rs104894953 GRCh38 Chromosome X, 37728068: 37728068
10 XK NM_021083.3(XK): c.895C> T (p.Gln299Ter) single nucleotide variant Pathogenic rs104894954 GRCh37 Chromosome X, 37587275: 37587275
11 XK NM_021083.3(XK): c.895C> T (p.Gln299Ter) single nucleotide variant Pathogenic rs104894954 GRCh38 Chromosome X, 37728022: 37728022

Expression for Mcleod Syndrome

Search GEO for disease gene expression data for Mcleod Syndrome.

Pathways for Mcleod Syndrome

GO Terms for Mcleod Syndrome

Cellular components related to Mcleod Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sarcolemma GO:0042383 9.26 DMD SGCA
2 synaptic vesicle membrane GO:0030672 9.16 DMD DRD2
3 lateral plasma membrane GO:0016328 8.96 DMD DRD2
4 dystrophin-associated glycoprotein complex GO:0016010 8.62 DMD SGCA

Biological processes related to Mcleod Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 muscle organ development GO:0007517 9.37 DMD SGCA
2 locomotory behavior GO:0007626 9.32 DRD2 VPS13A
3 protein localization GO:0008104 9.26 DRD2 VPS13A
4 regulation of heart rate GO:0002027 9.16 DMD DRD2
5 skeletal muscle tissue regeneration GO:0043403 8.96 DMD SGCA
6 response to denervation involved in regulation of muscle adaptation GO:0014894 8.62 DMD SGCA

Sources for Mcleod Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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