Pantothenate kinase-associated neurodegeneration

General Information (adopted from Orphanet):

Synonyms, Signs: PANTOTHENATE KINASE-ASSOCIATED NEURODEGENERATION
HALLERVORDEN-SPATZ DISEASE
PKAN NEUROAXONAL DYSTROPHY, JUVENILE-ONSET
PKAN
NBIA1
Neurodegeneration with brain iron accumulation type 1
Hallervorden-Spatz syndrome
Number of Symptoms 78
OrphanetNr: 157850
OMIM Id: 234200
ICD-10: G23.0
UMLs:
MeSH: D006211
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: All ages
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of other vitamins and cofactors metabolism and transport
 -Rare genetic disease
Disorder of phospholipids, sphingolipids and fatty acids biosynthesis with central nervous system predominant involvement
 -Rare genetic disease
Metabolic disease with pigmentary retinitis
 -Rare eye disease
 -Rare genetic disease
Neuroacanthocytosis
 -Rare genetic disease
 -Rare neurologic disease
Neurodegeneration with brain iron accumulation
 -Rare genetic disease
 -Rare neurologic disease
Syndromic retinitis pigmentosa
 -Rare eye disease
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
(HPO:0002019) Constipation Frequent [Orphanet] 194 / 7739
2
(HPO:0011968) Feeding difficulties 240 / 7739
3
(HPO:0008872) Feeding difficulties in infancy 153 / 7739
4
(HPO:0000648) Optic atrophy 238 / 7739
5
(HPO:0000510) Rod-cone dystrophy Very frequent [Orphanet] 266 / 7739
6
(HPO:0000580) Pigmentary retinopathy 49 / 7739
7
(HPO:0000546) Retinal degeneration 61 / 7739
8
(HPO:0000505) Visual impairment Occasional [Orphanet] 297 / 7739
9
(HPO:0002205) Recurrent respiratory infections Frequent [Orphanet] 254 / 7739
10
(HPO:0001618) Dysphonia 28 / 7739
11
(HPO:0004325) Decreased body weight Occasional [Orphanet] 492 / 7739
12
(HPO:0004326) Cachexia Occasional [Orphanet] 71 / 7739
13
(HPO:0001927) Acanthocytosis 11 / 7739
14
(HPO:0003199) Decreased muscle mass 27 / 7739
15
(HPO:0003198) Myopathy 151 / 7739
16
(HPO:0004305) Involuntary movements Frequent [Orphanet] 50 / 7739
17
(HPO:0001266) Choreoathetosis 57 / 7739
18
(HPO:0001291) Abnormality of the cranial nerves Frequent [Orphanet] 27 / 7739
19
(HPO:0001251) Ataxia 413 / 7739
20
(HPO:0002304) Akinesia 18 / 7739
21
(HPO:0002067) Bradykinesia 62 / 7739
22
(HPO:0002071) Abnormality of extrapyramidal motor function 76 / 7739
23
(HPO:0001300) Parkinsonism 75 / 7739
24
(HPO:0007256) Abnormal pyramidal signs 116 / 7739
25
(HPO:0001347) Hyperreflexia Frequent [Orphanet] 363 / 7739
26
(HPO:0001276) Hypertonia Frequent [Orphanet] 317 / 7739
27
(HPO:0001257) Spasticity 251 / 7739
28
(HPO:0000658) Eyelid apraxia 5 / 7739
29
(HPO:0002063) Rigidity 92 / 7739
30
(HPO:0000643) Blepharospasm 20 / 7739
31
(HPO:0001332) Dystonia 197 / 7739
32
(HPO:0000708) Behavioral abnormality Occasional [Orphanet] 212 / 7739
33
(HPO:0100851) Abnormal emotion/affect behavior Occasional [Orphanet] 85 / 7739
34
(HPO:0100033) Tics 6 / 7739
35
(HPO:0100034) Motor tics 5 / 7739
36
(HPO:0001260) Dysarthria 329 / 7739
37
(HPO:0000726) Dementia 131 / 7739
38
(HPO:0001268) Mental deterioration 88 / 7739
39
(HPO:0001263) Global developmental delay 853 / 7739
40
(HPO:0000716) Depression 99 / 7739
41
(HPO:0000722) Obsessive-compulsive behavior Occasional [Orphanet] 35 / 7739
42
(HPO:0008770) Obsessive-compulsive trait 6 / 7739
43
(HPO:0100543) Cognitive impairment Occasional [Orphanet] 230 / 7739
44
(HPO:0002167) Neurological speech impairment Occasional [Orphanet] 308 / 7739
45
(HPO:0100022) Abnormality of movement Very frequent [Orphanet] 129 / 7739
46
(HPO:0002310) Orofacial dyskinesia 10 / 7739
47
(HPO:0001288) Gait disturbance Very frequent [Orphanet] 318 / 7739
48
(HPO:0000752) Hyperactivity 140 / 7739
49
(HPO:0001337) Tremor Frequent [Orphanet] 200 / 7739
50
(HPO:0002015) Dysphagia Frequent [Orphanet] 301 / 7739
51
(HPO:0001250) Seizures Occasional [Orphanet] 1245 / 7739
52
(HPO:0001760) Abnormality of the foot Frequent [Orphanet] 96 / 7739
53
(HPO:0001367) Abnormal joint morphology Occasional [Orphanet] 53 / 7739
54
(HPO:0002577) Abnormality of the stomach Frequent [Orphanet] 84 / 7739
55
(HPO:0000273) Facial grimacing 6 / 7739
56
(HPO:0003011) Abnormality of the musculature Occasional [Orphanet] 47 / 7739
57
(HPO:0001000) Abnormality of skin pigmentation Occasional [Orphanet] 105 / 7739
58
(HPO:0000953) Hyperpigmentation of the skin 75 / 7739
59
(HPO:0000020) Urinary incontinence 75 / 7739
60
(HPO:0030089) Abnormal muscle fiber protein expression Occasional [Orphanet] 64 / 7739
61
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739
62
(HPO:0007313) Cerebral degeneration 4 / 7739
63
(HPO:0002454) Eye of the tiger anomaly of globus pallidus 3 / 7739
64
(HPO:0002283) Global brain atrophy 12 / 7739
65
(HPO:0002180) Neurodegeneration 31 / 7739
66
(HPO:0003678) Rapidly progressive 33 / 7739
67
(MedDRA:10021639) Incontinence 11 / 7739
68
(OMIM) 'Stiffness' 5 / 7739
69
(OMIM) Apraxia of eyelid opening 1 / 7739
70
(OMIM) Axonal 'spheroid' inclusions in the CNS 1 / 7739
71
(OMIM) Axonal swelling or thickening in the CNS 1 / 7739
72
(OMIM) Difficulty writing 2 / 7739
73
(OMIM) Iron deposits in the globus pallidus, caudate, and substantia nigra 1 / 7739
74
(OMIM) MRI shows decreased signal intensity in the pallidal nuclei with central hyperintensity ('eye of the tiger' sign) 2 / 7739
75
(OMIM) Myopathic changes on pathology 1 / 7739
76
(OMIM) Psychiatric abnormalities (more common in patients with atypical disease and slow progression) 3 / 7739
77
(OMIM) Speech abnormalities 3 / 7739
78
(OMIM) Walking on toes 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Neurodegeneration with brain iron accumulation is a genetically heterogeneous disorder characterized by progressive iron accumulation in the basal ganglia and other regions of the brain, resulting in extrapyramidal movements, such as parkinsonism and dystonia. Age at onset, severity, ...
Diagnosis OMIM - Differential Diagnosis

Using single photon emission computed tomography (SPECT), Cossu et al. (2005) found normal striatal presynaptic dopamine activity in 2 sibs with PKAN confirmed by genetic analysis. The authors suggested that these SPECT findings, ...

Clinical Description OMIM The original description of this syndrome by Hallervorden and Spatz (1922) concerned a sibship of 12 in which 5 sisters showed clinically increasing dysarthria and progressive dementia, and at autopsy brown discoloration of the globus pallidus and substantia ...
Genotype-Phenotype Correlations OMIM Hayflick et al. (2003) studied 123 patients from 98 families with a diagnosis of Hallervorden-Spatz syndrome and classified them as having classic disease or atypical disease. All patients with classic Hallervorden-Spatz syndrome and one-third of those with atypical ...
Molecular genetics OMIM In affected members of an Amish family with Hallervorden-Spatz syndrome, Zhou et al. (2001) identified a homozygous 7-bp deletion (606157.0001) in the coding sequence of the PANK2 gene. Additional missense and null mutations in the PANK2 gene were ...
Population genetics OMIM In affected members from 4 Dutch families with pantothenate kinase-associated neurodegeneration, Rump et al. (2005) identified a 3-bp deletion in the PANK2 gene (606157.0014). Haplotype analysis suggested a founder effect that arose in Friesland, a northern province of ...
Diagnosis GeneReviews Suspicion of pantothenate kinase-associated neurodegeneration (PKAN) often arises when characteristic magnetic resonance imaging (MRI) changes are demonstrated in an individual with suggestive clinical features. Following the discovery of PANK2 [Zhou et al 2001], Hayflick et al [2003] delineated two clinical forms of PKAN, the classic form and an atypical form, based on age at onset and rate of disease progression....
Clinical Description GeneReviews Classic PKAN. The neurologic signs and symptoms of early-onset, rapidly progressive (classic) pantothenate kinase-associated neurodegeneration (PKAN) are primarily extrapyramidal and include dystonia, dysarthria, and rigidity. ...
Genotype-Phenotype Correlations GeneReviews A clear genotype-phenotype correlation for PKAN has not been observed....
Differential Diagnosis GeneReviews Neurodegeneration with brain iron accumulation multi-gene panels may include testing for a number of the genes associated with disorders discussed in this section. Note: The genes included and the methods used in multi-gene panels vary by laboratory and over time; a panel may not include a specific gene of interest....
Management GeneReviews To establish the extent of disease in an individual diagnosed with pantothenate kinase-associated neurodegeneration (PKAN), 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....