MCLDS
MCID: MCL009
MIFTS: 45

Mcleod Syndrome (MCLDS)

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

Aliases & Classifications for Mcleod Syndrome

MalaCards integrated aliases for Mcleod Syndrome:

Name: Mcleod Syndrome 57 12 73 20 43 72 36
Mcleod Neuroacanthocytosis Syndrome 12 25 20 43 58 29 6
Mcleod Syndrome with or Without Chronic Granulomatous Disease 57 12 13
X-Linked Mcleod Syndrome 12 20 58
Mls 12 58 72
Neuroacanthocytosis, Mcleod Type 57 44
Mcleod Phenotype 57 72
Mcleod Syndrome with Chronic Granulomatous Disease 72
Mcleod Type Neuroacanthocytosis 12
Neuroacanthocytosis Mcleod Type 72
Blood Group Deletion Syndrome 70
Syndrome, Mcleod 39
Mclds 57

Characteristics:

Orphanet epidemiological data:

58
mcleod neuroacanthocytosis syndrome
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM®:

57 (Updated 05-Apr-2021)
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:

31
mcleod syndrome:
Inheritance x-linked inheritance


GeneReviews:

25
Penetrance In males, the penetrance of neurologic and neuromuscular manifestations of mls is high – perhaps even complete – after age 50 years. available data indicate that most males with the mcleod blood group phenotype will develop clinical manifestations 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 manifestations may be absent or only minor even after long-term follow up [jung et al 2003, walker et al 2007b]....

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare haematological diseases


Summaries for Mcleod Syndrome

MedlinePlus Genetics : 43 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.McLeod neuroacanthocytosis syndrome affects the brain and spinal cord (central nervous system). Affected individuals have involuntary movements, including jerking motions (chorea), particularly of the arms and legs, and muscle tensing (dystonia) in the face and throat, which can cause grimacing and vocal tics (such as grunting and clicking noises). Dystonia of the tongue can lead to swallowing difficulties. Seizures occur in approximately half of all people with McLeod neuroacanthocytosis syndrome. Individuals with this condition may develop difficulty processing, learning, and remembering information (cognitive impairment). They may also develop psychiatric disorders, such as depression, bipolar disorder, psychosis, or obsessive-compulsive disorder.People with McLeod neuroacanthocytosis syndrome also have problems with their muscles, including muscle weakness (myopathy) and muscle degeneration (atrophy). Sometimes, nerves that connect to muscles atrophy (neurogenic atrophy), leading to loss of muscle mass and impaired movement. Individuals with McLeod neuroacanthocytosis syndrome may also have reduced sensation and weakness in their arms and legs (peripheral neuropathy). Life-threatening heart problems such as irregular heartbeats (arrhythmia) and a weakened and enlarged heart (dilated cardiomyopathy) are common in individuals with this disorder.The signs and symptoms of McLeod neuroacanthocytosis syndrome usually begin in mid-adulthood. Behavioral changes, such as lack of self-restraint, the inability to take care of oneself, anxiety, depression, and changes in personality may be the first signs of this condition. While these behavioral changes are typically not progressive, the movement and muscle problems and intellectual impairments tend to worsen with age.

MalaCards based summary : Mcleod Syndrome, also known as mcleod neuroacanthocytosis syndrome, is related to choreoacanthocytosis and choreatic disease. An important gene associated with Mcleod Syndrome is XK (X-Linked Kx Blood Group). Affiliated tissues include heart, spinal cord and tongue, and related phenotypes are acanthocytosis and hepatosplenomegaly

Disease Ontology : 12 A neuroacanthocytosis characterized by absence of red blood cell Kx antigen, weak expression of Kell red blood cell antigens, acanthocytosis, compensated hemolysis, and involuntary movements that has material basis in mutation in XK on chromosome Xp21.1.

GARD : 20 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.

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) (Updated 05-Apr-2021)

KEGG : 36 McLeod syndrome is an X-linked multisystem disorder including the CNS (chorea, epilepsy), the PNS (axonal polyneuropathy), and the blood cells (acanthocytosis of the erythrocytes) characterized by late onset abnormalities in the neuromuscular and hematopoietic systems. Mild myopathy is a common manifestation in most cases. Patients often present with mild, asymptomatic hyperCKemia. The absence of the XK membrane transport protein seems to be causative.

UniProtKB/Swiss-Prot : 72 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.

Wikipedia : 73 McLeod syndrome (pronounced /məˈklaʊd/) is an X-linked recessive genetic disorder that may affect the... 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 152)
# Related Disease Score Top Affiliating Genes
1 choreoacanthocytosis 32.0 XK VPS13A
2 choreatic disease 30.4 XK VPS13A DRD2
3 huntington disease 30.0 XK VPS13A DRD2
4 muscular dystrophy 29.9 SGCA DMD CKM
5 movement disease 29.5 VPS13A DRD2
6 muscular disease 29.5 SGCA DMD
7 lingual-facial-buccal dyskinesia 29.4 XK VPS13A DRD2
8 muscular dystrophy, duchenne type 29.4 XK SGCA DMD CKM
9 myopathy 29.2 XK VPS13A SGCA DMD CKM
10 dilated cardiomyopathy 29.1 XK SGCA DMD CKM
11 linear skin defects with multiple congenital anomalies 1 11.7
12 mohr-tranebjaerg syndrome 11.3
13 o'sullivan-mcleod syndrome 11.3
14 renal tubular dysgenesis 11.2
15 mucolipidoses 11.1
16 abetalipoproteinemia 10.7
17 chorea, childhood-onset, with psychomotor retardation 10.6
18 microphthalmia 10.5
19 chronic granulomatous disease 10.4
20 muscular atrophy 10.3
21 blood group--kell system 10.2
22 sclerocornea 10.2
23 retinitis pigmentosa 10.2
24 neuroretinitis 10.2
25 retinitis 10.2
26 basal ganglia disease 10.1
27 polyneuropathy 10.1
28 personality disorder 10.1
29 tic disorder 10.1
30 progressive muscular atrophy 10.1
31 focal dermal hypoplasia 10.0
32 obsessive-compulsive disorder 10.0
33 granulomatous disease, chronic, x-linked 10.0
34 polymyositis 10.0
35 spinal muscular atrophy 10.0
36 motor neuron disease 10.0
37 axonal neuropathy 10.0
38 neuropathy 10.0
39 aicardi syndrome 9.9
40 fryns microphthalmia syndrome 9.9
41 graft-versus-host disease 9.9
42 mulchandani-bhoj-conlin syndrome 9.9
43 ocular albinism 9.9
44 severe combined immunodeficiency 9.9
45 albinism 9.9
46 aspergillosis 9.9
47 invasive aspergillosis 9.9
48 amyotrophic lateral sclerosis 1 9.9
49 atrial standstill 1 9.9
50 cardiac conduction defect 9.9

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



Diseases related to Mcleod Syndrome

Symptoms & Phenotypes for Mcleod Syndrome

Human phenotypes related to Mcleod Syndrome:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 acanthocytosis 31 obligate (100%) HP:0001927
2 hepatosplenomegaly 31 occasional (7.5%) HP:0001433
3 rhabdomyolysis 31 occasional (7.5%) HP:0003201
4 depressivity 31 HP:0000716
5 dysarthria 31 HP:0001260
6 muscle weakness 31 HP:0001324
7 dyskinesia 31 HP:0100660
8 myopathy 31 HP:0003198
9 anxiety 31 HP:0000739
10 elevated serum creatine kinase 31 HP:0003236
11 dilated cardiomyopathy 31 HP:0001644
12 obsessive-compulsive behavior 31 HP:0000722
13 areflexia 31 HP:0001284
14 cardiomyopathy 31 HP:0001638
15 atrial fibrillation 31 HP:0005110
16 generalized-onset seizure 31 HP:0002197
17 motor axonal neuropathy 31 HP:0007002
18 personality disorder 31 HP:0012075

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
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)

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

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

Abdomen Spleen:
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)

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

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 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Mcleod Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.43 CKM DMD DRD2 SGCA VPS13A XK
2 muscle MP:0005369 9.02 CKM DMD DRD2 SGCA XK

Drugs & Therapeutics for Mcleod Syndrome

Search Clinical Trials , NIH Clinical Center for Mcleod Syndrome

Cochrane evidence based reviews: neuroacanthocytosis, mcleod type

Genetic Tests for Mcleod Syndrome

Genetic tests related to Mcleod Syndrome:

# Genetic test Affiliating Genes
1 Mcleod Neuroacanthocytosis Syndrome 29

Anatomical Context for Mcleod Syndrome

MalaCards organs/tissues related to Mcleod Syndrome:

40
Heart, Spinal Cord, Tongue, Lung, Brain, Skeletal Muscle

Publications for Mcleod Syndrome

Articles related to Mcleod Syndrome:

(show top 50) (show all 195)
# Title Authors PMID Year
1
McLeod neuroacanthocytosis: genotype and phenotype. 61 6 57 25
11761473 2001
2
Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein. 61 25 6 57
8004674 1994
3
A new phenotype (McLeod) in the Kell blood-group system. 6 25 57
13860532 1961
4
McLeod syndrome: a neurohaematological disorder. 25 57 61
17683354 2007
5
A spontaneous novel XK gene mutation in a patient with McLeod syndrome. 6 25 61
11703337 2001
6
McLeod syndrome: a novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings. 25 61 6
11261514 2001
7
A novel point mutation in the McLeod syndrome gene in neuroacanthocytosis. 61 6 25
8619554 1996
8
Benign X-linked myopathy with acanthocytes (McLeod syndrome). Its relationship to X-linked muscular dystrophy. 61 57 25
6685553 1983
9
Localization of the McLeod locus (XK) within Xp21 by deletion analysis. 25 57
3358422 1988
10
Hereditary acanthocytosis associated with the McLeod phenotype of the Kell blood group system. 25 57
476009 1979
11
A novel frameshift mutation in the McLeod syndrome gene in a Japanese family. 61 6
10426139 1999
12
Atypical McLeod syndrome manifested as X-linked chorea-acanthocytosis, neuromyopathy and dilated cardiomyopathy: report of a family. 61 57
7931427 1994
13
Gene deletion in a patient with chronic granulomatous disease and McLeod syndrome: fine mapping of the Xk gene locus. 61 57
3334897 1988
14
Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. 61 57
4039107 1985
15
Elevated serum creatine phosphokinase in subjects with McLeod syndrome. 61 57
7197431 1981
16
Life expectancy and mortality in chorea-acanthocytosis and McLeod syndrome. 61 25
30245172 2019
17
Molecular Basis and Clinical Overview of McLeod Syndrome Compared With Other Neuroacanthocytosis Syndromes: A Review. 25 61
30128557 2018
18
WITHDRAWN: Novel Xp21.1 deletion associated with unusual features in a large McLeod syndrome kindred. 25 61
30305234 2018
19
Stepwise partitioning of Xp21: a profiling method for XK deletions causative of the McLeod syndrome. 61 25
28555782 2017
20
Neurodegeneration in the elderly - When the blood type matters: An overview of the McLeod syndrome with focus on hematological features. 25 61
25934153 2015
21
Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis. 25 61
23122227 2013
22
Neuroacanthocytosis syndromes. 61 25
22027213 2011
23
Feeding dystonia in McLeod syndrome. 25 61
21714011 2011
24
Head drops are also observed in McLeod syndrome. 25 61
21469202 2011
25
Evolution of striatal degeneration in McLeod syndrome. 25 61
19968700 2010
26
Cardiac abnormalities in McLeod syndrome. 61 25
18045706 2009
27
McLeod myopathy revisited: more neurogenic and less benign. 61 25
18055495 2007
28
Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases. 25 61
17300882 2007
29
Expression profiles of mouse Kell, XK, and XPLAC mRNA. 25 61
17189525 2007
30
McLeod phenotype without the McLeod syndrome. 25 61
17302777 2007
31
Phenotypic variation among brothers with the McLeod neuroacanthocytosis syndrome. 25 61
17133513 2007
32
Cerebral metabolic alterations in McLeod syndrome. 61 25
16914926 2006
33
Neuroacanthocytosis: new developments in a neglected group of dementing disorders. 61 25
15760637 2005
34
Testing for acanthocytosis A prospective reader-blinded study in movement disorder patients. 25 61
15654559 2005
35
Schizophrenia as a manifestation of X-linked Mcleod-Neuroacanthocytosis syndrome. 25 61
15163264 2004
36
McLeod syndrome resulting from a novel XK mutation. 61 25
12899725 2003
37
McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement. 61 25
12823753 2003
38
Kell and XK immunohistochemistry in McLeod myopathy. 61 25
11562915 2001
39
The chorea of McLeod syndrome. 25 61
11746618 2001
40
Reduction of striatal glucose metabolism in McLeod choreoacanthocytosis. 61 25
11254778 2001
41
McLeod syndrome and neuroacanthocytosis with a novel mutation in the XK gene. 61 25
11104227 2000
42
Muscle CT scan findings in McLeod syndrome and chorea-acanthocytosis. 61 25
10883007 2000
43
Analysis of deletions in three McLeod patients: exclusion of the XS locus from the Xp21.1-Xp21.2 region. 25 61
10651848 2000
44
A case of McLeod syndrome with unusually severe myopathy. 25 61
10465497 1999
45
Association of XK and Kell blood group proteins. 25 61
9593744 1998
46
A method to detect McLeod phenotype red blood cells. 25 61
15387728 1996
47
Cerebral involvement in McLeod syndrome. 25 61
8290045 1994
48
McLeod syndrome: a distinct form of neuroacanthocytosis. Report of two cases and literature review with emphasis on neuromuscular manifestations. 61 25
1512605 1992
49
Cardiomyopathy associated with the syndrome of amyotrophic chorea and acanthocytosis. 57
7073157 1982
50
Kx: its relationship to chronic granulomatous disease and genetic linkage with Xg. 57
7236890 1981

Variations for Mcleod Syndrome

ClinVar genetic disease variations for Mcleod Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 XK XK, 1-BP DEL Deletion Pathogenic 9766 GRCh37:
GRCh38:
2 XK XK, 13-BP DEL Deletion Pathogenic 9769 GRCh37:
GRCh38:
3 XK NM_021083.4(XK):c.508+1G>A SNV Pathogenic 9764 rs1602145991 GRCh37: X:37553802-37553802
GRCh38: X:37694549-37694549
4 XK NM_021083.4(XK):c.509-1G>A SNV Pathogenic 9765 rs1602158863 GRCh37: X:37586888-37586888
GRCh38: X:37727635-37727635
5 XK NM_021083.4(XK):c.1013del (p.Phe338fs) Deletion Pathogenic 9767 rs1602159120 GRCh37: X:37587390-37587390
GRCh38: X:37728137-37728137
6 XK NM_021083.4(XK):c.880T>C (p.Cys294Arg) SNV Pathogenic 9768 rs28933690 GRCh37: X:37587260-37587260
GRCh38: X:37728007-37728007
7 XK NM_021083.4(XK):c.941G>A (p.Trp314Ter) SNV Pathogenic 9770 rs104894953 GRCh37: X:37587321-37587321
GRCh38: X:37728068-37728068
8 XK NM_021083.4(XK):c.895C>T (p.Gln299Ter) SNV Pathogenic 9771 rs104894954 GRCh37: X:37587275-37587275
GRCh38: X:37728022-37728022

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

72
# 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

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 SGCA DMD
2 synaptic vesicle membrane GO:0030672 9.16 DRD2 DMD
3 lateral plasma membrane GO:0016328 8.96 DRD2 DMD
4 dystrophin-associated glycoprotein complex GO:0016010 8.62 SGCA DMD

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 SGCA DMD
2 locomotory behavior GO:0007626 9.32 VPS13A DRD2
3 protein localization GO:0008104 9.26 VPS13A DRD2
4 regulation of heart rate GO:0002027 9.16 DRD2 DMD
5 skeletal muscle tissue regeneration GO:0043403 8.96 SGCA DMD
6 response to denervation involved in regulation of muscle adaptation GO:0014894 8.62 SGCA DMD

Sources for Mcleod Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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