McLeod neuroacanthocytosis syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: MCLDS
MLS
McLeod phenotype
Neuroacanthocytosis, McLeod type McLeod syndrome with chronic granulomatous disease, included
X-linked McLeod syndrome
Number of Symptoms 93
OrphanetNr: 59306
OMIM Id: 300842
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 150 cases
Inheritance: X-linked
17683354 [IBIS]
Age of onset: Adult
17683354 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Constitutional hemolytic anemia due to acanthocytosis
 -Rare genetic disease
 -Rare hematologic disease
Neuroacanthocytosis
 -Rare genetic disease
 -Rare neurologic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
Other metabolic disease with epilepsy
 -Rare neurologic disease
Syndrome associated with dilated cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease

Comment:

McLeod phenotype is caused by mutation in the XK gene (OMIM). Patients with MLS usually show a slow progression of disease with a mean onset between 30 and 40 years of age (PMID:17683354). There is no clear phenotype-genotype correlation, and symptoms can vary significantly within families (PMID:26090076).

Symptom Information: Sort by abundance 

1
(HPO:0002094) Dyspnea 7931427 IBIS 132 / 7739
2
(HPO:0004322) Short stature 7931427 IBIS 1232 / 7739
3
(HPO:0001712) Left ventricular hypertrophy 7931427 IBIS 76 / 7739
4
(HPO:0001638) Cardiomyopathy Frequent [IBIS] 17683354; 7931427; 26090076 IBIS 192 / 7739
5
(HPO:0001644) Dilated cardiomyopathy 17683354; 7931427 IBIS 141 / 7739
6
(HPO:0011675) Arrhythmia 26090076 IBIS 226 / 7739
7
(HPO:0005110) Atrial fibrillation 17683354; 11761473 IBIS 71 / 7739
8
(HPO:0004755) Supraventricular tachycardia 17683354 IBIS 20 / 7739
9
(HPO:0004308) Ventricular arrhythmia 7931427 IBIS 46 / 7739
10
(HPO:0006682) Ventricular extrasystoles 7931427 IBIS 25 / 7739
11
(HPO:0001663) Ventricular fibrillation 7931427 IBIS 35 / 7739
12
(HPO:0011713) Left bundle branch block 7931427 IBIS 30 / 7739
13
(HPO:0001695) Cardiac arrest 7931427 IBIS 87 / 7739
14
(HPO:0001635) Congestive heart failure 17683354 IBIS 232 / 7739
15
(HPO:0003236) Elevated serum creatine phosphokinase Frequent [IBIS] 17683354; 11761473; 1998879; 7931427; 26090076 IBIS 214 / 7739
16
(HPO:0001903) Anemia 11761473 IBIS 289 / 7739
17
(HPO:0001878) Hemolytic anemia 11761473 IBIS 83 / 7739
18
(HPO:0010970) Blood group antigen abnormality Frequent [IBIS] 17683354; 11761473; 7931427; 26090076 IBIS 4 / 7739
19
(HPO:0001927) Acanthocytosis Frequent [IBIS] obligate [HPO:skoehler] 17683354; 11761473; 1998879; 7931427; 26090076 IBIS 11 / 7739
20
(HPO:0009055) Generalized limb muscle atrophy 17683354 IBIS 4 / 7739
21
(HPO:0003198) Myopathy 17683354; 26090076 IBIS 151 / 7739
22
(HPO:0003201) Rhabdomyolysis 17683354; 26090076 IBIS 27 / 7739
23
(HPO:0003750) Increased muscle fatiguability 11761473 IBIS 8 / 7739
24
(HPO:0004305) Involuntary movements 17683354; 7931427 IBIS 50 / 7739
25
(HPO:0002072) Chorea 17683354; 11761473; 1998879; 7931427; 26090076 IBIS 53 / 7739
26
(HPO:0001324) Muscle weakness 17683354; 7931427 IBIS 859 / 7739
27
(HPO:0007340) Lower limb muscle weakness 26090076 IBIS 61 / 7739
28
(HPO:0007002) Motor axonal neuropathy 17683354 IBIS 17 / 7739
29
(HPO:0007141) Sensorimotor neuropathy Frequent [IBIS] 26090076 IBIS 27 / 7739
30
(HPO:0000763) Sensory neuropathy 26090076 IBIS 78 / 7739
31
(HPO:0003401) Paresthesia Rare [IBIS] 11761473 IBIS 42 / 7739
32
(HPO:0007328) Impaired pain sensation Rare [IBIS] 11761473 IBIS 10 / 7739
33
(HPO:0010829) Impaired temperature sensation Rare [IBIS] 11761473 IBIS 5 / 7739
34
(HPO:0002166) Impaired vibration sensation in the lower limbs 17683354; 11761473 IBIS 26 / 7739
35
(HPO:0003390) Sensory axonal neuropathy 17683354 IBIS 26 / 7739
36
(HPO:0009830) Peripheral neuropathy 26090076 IBIS 206 / 7739
37
(HPO:0001300) Parkinsonism 26090076 IBIS 75 / 7739
38
(HPO:0003487) Babinski sign 1998879 IBIS 179 / 7739
39
(HPO:0001276) Hypertonia 7931427 IBIS 317 / 7739
40
(HPO:0002063) Rigidity Rare [IBIS] 11761473 IBIS 92 / 7739
41
(HPO:0001332) Dystonia 11761473; 26090076 IBIS 197 / 7739
42
(HPO:0000708) Behavioral abnormality 1998879; 7931427 IBIS 212 / 7739
43
(HPO:0000712) Emotional lability 11761473 IBIS 44 / 7739
44
(HPO:0012433) Abnormal social behavior 11761473 IBIS 7 / 7739
45
(HPO:0000711) Restlessness 17683354 IBIS 18 / 7739
46
(HPO:0000739) Anxiety 17683354; 11761473; 7931427 IBIS 67 / 7739
47
(HPO:0007302) Bipolar affective disorder 17683354 IBIS 15 / 7739
48
(HPO:0100033) Tics 1998879; 26090076 IBIS 6 / 7739
49
(HPO:0001260) Dysarthria 17683354; 11761473; 1998879; 7931427 IBIS 329 / 7739
50
(HPO:0001289) Confusion 7931427 IBIS 36 / 7739
51
(HPO:0000726) Dementia 17683354; 1998879 IBIS 131 / 7739
52
(HPO:0001268) Mental deterioration 17683354 IBIS 88 / 7739
53
(HPO:0000716) Depression 17683354; 11761473; 7931427 IBIS 99 / 7739
54
(HPO:0000738) Hallucinations 7931427 IBIS 60 / 7739
55
(HPO:0000722) Obsessive-compulsive behavior 17683354 IBIS 35 / 7739
56
(HPO:0000751) Personality changes 1998879 IBIS 33 / 7739
57
(HPO:0012075) Personality disorder 17683354 IBIS 4 / 7739
58
(HPO:0100785) Insomnia 11761473; 7931427 IBIS 18 / 7739
59
(HPO:0010535) Sleep apnea 11761473 IBIS 24 / 7739
60
(HPO:0100543) Cognitive impairment 11761473 IBIS 230 / 7739
61
(HPO:0002354) Memory impairment 17683354 IBIS 63 / 7739
62
(HPO:0100022) Abnormality of movement Frequent [IBIS] 11761473; 1998879; 26090076 IBIS 129 / 7739
63
(HPO:0100660) Dyskinesia 7931427 IBIS 19 / 7739
64
(HPO:0002310) Orofacial dyskinesia 17683354; 11761473; 1998879 IBIS 10 / 7739
65
(HPO:0001288) Gait disturbance 7931427 IBIS 318 / 7739
66
(HPO:0002015) Dysphagia Rare [IBIS] 11761473; 7931427 IBIS 301 / 7739
67
(HPO:0001284) Areflexia Frequent [IBIS] 17683354; 11761473; 1998879; 7931427; 26090076 IBIS 198 / 7739
68
(HPO:0002600) Hyporeflexia of lower limbs 7931427 IBIS 13 / 7739
69
(HPO:0012391) Hyporeflexia of upper limbs 7931427 IBIS 2 / 7739
70
(HPO:0001250) Seizures Frequent [IBIS] 1998879; 26090076 IBIS 1245 / 7739
71
(HPO:0002197) Generalized seizures 17683354; 11761473 IBIS 30 / 7739
72
(HPO:0000975) Hyperhidrosis 11761473 IBIS 64 / 7739
73
(HPO:0002607) Bowel incontinence 11761473 IBIS 33 / 7739
74
(HPO:0002910) Elevated hepatic transaminases 26090076 IBIS 158 / 7739
75
(HPO:0002240) Hepatomegaly 11761473; 26090076 IBIS 467 / 7739
76
(HPO:0001433) Hepatosplenomegaly 17683354 IBIS 78 / 7739
77
(HPO:0001744) Splenomegaly 11761473; 26090076 IBIS 337 / 7739
78
(HPO:0100247) Recurrent singultus Rare [IBIS] 11761473 IBIS 7 / 7739
79
(HPO:0005346) Abnormal facial expression Rare [IBIS] 11761473 IBIS 2 / 7739
80
(HPO:0003781) Excessive salivation Rare [IBIS] 11761473 IBIS 15 / 7739
81
(HPO:0045040) Abnormal lactate dehydrogenase activity 11761473 IBIS 1 / 7739
82
(HPO:0100707) Abnormality of the astrocytes 17683354 IBIS 1 / 7739
83
(HPO:0002500) Abnormality of the cerebral white matter 26090076 IBIS 73 / 7739
84
(HPO:0010994) Abnormality of the striatum 17683354; 26090076 IBIS 2 / 7739
85
(HPO:0002340) Caudate atrophy 17683354; 1998879; 7931427; 26090076 IBIS 4 / 7739
86
(HPO:0002059) Cerebral atrophy 1998879 IBIS 171 / 7739
87
(HPO:0002529) Neuronal loss in central nervous system 17683354; 26090076 IBIS 37 / 7739
88
(MedDRA:10001551) Alanine aminotransferase increased 11761473 IBIS 4 / 7739
89
(MedDRA:10003481) Aspartate aminotransferase increased 11761473 IBIS 4 / 7739
90
(MedDRA:10017693) Gamma-glutamyltransferase increased 11761473 IBIS 2 / 7739
91
(MedDRA:10019150) Haptoglobin decreased 11761473 IBIS 1 / 7739
92
(MedDRA:10050467) Tongue biting 11761473 IBIS 1 / 7739
93
(OMIM) Elevated lactate dehydrogenase 11761473 IBIS 4 / 7739

Associated genes:

XK;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
XK rs104894953 pathogenic RCV000010424.4
XK rs104894954 pathogenic RCV000010425.3
XK rs28933690 pathogenic RCV000010422.2

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM The McLeod phenotype was described by Allen et al. (1961) in a man of that surname. His red cells showed unaccountably weak reactivity to Kell antisera. In 1970, his red cells were noted to be acanthocytic in the ...
Molecular genetics OMIM Using nucleotide sequence analysis of the XK gene in 2 unrelated patients with McLeod syndrome, Ho et al. (1994) demonstrated point mutations at invariant residues of 5-prime and 3-prime donor sites (e.g., 314850.0001).

Danek et al. ...

Diagnosis GeneReviews Diagnosis of McLeod neuroacanthocytosis syndrome (MLS) is established in individuals with the following combination of manifestations: ...
Clinical Description GeneReviews McLeod neuroacanthocytosis syndrome (MLS) is a multisystem disorder with central nervous system (CNS), neuromuscular, and hematologic manifestations in males. CNS manifestations of MLS resemble Huntington disease. Symptoms comprise the prototypic triad of a progressive neurodegenerative basal ganglia disease including (1) movement disorder, (2) cognitive alterations, and (3) psychiatric symptoms [Danek et al 2001a, Jung et al 2007]. It should be noted that each sign and symptom may develop in isolation or in variable combinations....
Genotype-Phenotype Correlations GeneReviews Data presently available are insufficient to draw conclusions about genotype-phenotype correlations in McLeod neuroacanthocytosis syndrome [Danek et al 2001a]. MLS shows considerable phenotypic variability, even between family members with identical XK mutations [Danek et al 2001b, Walker et al 2007b]. ...
Differential Diagnosis GeneReviews Hutington disease (HD). HD is the prototypic hereditary chorea syndrome and manifests with progressive movement disorder and cognitive and psychiatric disturbances. The mean age of onset of HD ranges from 35 to 44 years, and the median survival is 15 to 18 years after onset. The symptoms of HD and MLS may appear indistinguishable. However, autosomal dominant inheritance and anticipation in HD and the presence of seizures, elevated serum CK concentrations, and myopathy in MLS may help distinguish the two conditions. Diagnosis of HD rests on the detection of an expansion of the CAG trinucleotide repeat in HTT. ...
Management GeneReviews To establish the extent of disease in an individual diagnosed with McLeod neuroacanthocytosis syndrome (MLS), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....