Wilson disease

General Information (adopted from Orphanet):

Synonyms, Signs: HLD [IBIS]
WD
WND
hepatolenticular degeneration
Wilson&#39
s disease [IBIS]
Number of Symptoms 106
OrphanetNr: 905
OMIM Id: 277900
ICD-10: E83.0
UMLs:
MeSH:
MedDRA:
Snomed: 88518009

Prevalence, inheritance and age of onset:

Prevalence: <= 9 of 100 000
Inheritance: Autosomal recessive
27103860 [IBIS]
Age of onset: Childhood
27103860 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of copper metabolism
 -Rare genetic disease
Metabolic disease with cataract
 -Rare eye disease
 -Rare genetic disease
Metabolic disease with corneal opacity
 -Rare eye disease
 -Rare genetic disease
Metabolic liver disease
 -Rare genetic disease
 -Rare hepatic disease
Metal transport or utilization disorder with epilepsy
 -Rare neurologic disease
Nephropathy secondary to a storage or other metabolic disease
 -Rare genetic disease
 -Rare renal disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
Rare disorder with dystonia and other neurologic or systemic manifestation
 -Rare neurologic disease
Rare genetic tremor disorder
 -Rare genetic disease
Rare hereditary metabolic disease with peripheral neuropathy
 -Rare genetic disease
 -Rare neurologic disease
Rare neurologic disease with psychiatric involvement
 -Rare neurologic disease
Rare tremor disorder
 -Rare neurologic disease
Supranuclear oculomotor palsy
 -Rare eye disease
 -Rare genetic disease

Comment:

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism which leads to copper overload in different tissues of the body. The disorder of metabolism in patients with WD develops as a result of mutations in the adenosine triphosphatase 7B gene (ATP7B) located on the long arm of the 13th chromosome. More than 500 mutations of the ATP7B gene have been reported. Copper leads to tissue damage by accumulating in many organs including mainly the liver and brain as a result of lack of production of the proteins responsible of excretion of copper into the bile ducts in relation with these mutations. The incidence of WD is considered to be about 1/300000. Although the diagnosis of WD is made in the first decade of life in children, the neurological symptoms of WD are mostly observed in the second decade. Although WD is most frequently manifested with hepatic and neurological features related with chronic accumulation of copper, it has a wide clinical spectrum (PMID:27103860). It is now known that it is not the accumulation of copper itself what is deleterious to the organism, but rather free copper in the blood, which determines copper intoxication, as opposed to ceruloplasmin-bound copper (PMID:26692151). Patients with Wilson's disease have the autosomal recessive form of distal RTA (PMID:25120295). Short-term treatment of rats with Methanobactin (MB) efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD (PMID:27322060).

Symptom Information: Sort by abundance 

1
(HPO:0002013) Vomiting Frequent [IBIS] 50% (n=12) 27103860 IBIS 191 / 7739
2
(HPO:0200032) Kayser-Fleischer ring Frequent [IBIS] 50% (n=12) 27103860 IBIS 2 / 7739
3
(HPO:0000934) Chondrocalcinosis 3361541 IBIS 13 / 7739
4
(HPO:0008341) Distal renal tubular acidosis 25120295 IBIS 6 / 7739
5
(HPO:0001876) Pancytopenia 25910248 IBIS 89 / 7739
6
(HPO:0002150) Hypercalciuria 23087754 IBIS 45 / 7739
7
(HPO:0011016) Abnormality of urine glucose concentration Occasional [IBIS] 16% (n=25) 18661763 IBIS 1 / 7739
8
(HPO:0003076) Glycosuria Occasional [IBIS] 16% (n=25) 18661763 IBIS 32 / 7739
9
(HPO:0003355) Aminoaciduria 26692151 IBIS 65 / 7739
10
(HPO:0001638) Cardiomyopathy 26692151 IBIS 192 / 7739
11
(HPO:0011675) Arrhythmia 26692151 IBIS 226 / 7739
12
(HPO:0001279) Syncope Occasional [IBIS] 8% (n=12) 27103860 IBIS 94 / 7739
13
(HPO:0003073) Hypoalbuminemia Frequent [IBIS] 84% (n=12) 27103860 IBIS 40 / 7739
14
(HPO:0001928) Abnormality of coagulation Occasional [IBIS] 8% (n=12) 27103860 IBIS 44 / 7739
15
(HPO:0001903) Anemia Frequent [IBIS] 33% (n=12) 27103860 IBIS 289 / 7739
16
(HPO:0001878) Hemolytic anemia Rare [IBIS] 4% (n=25) 18661763 IBIS 83 / 7739
17
(HPO:0000969) Edema Occasional [IBIS] 20% (n=25) 18661763 IBIS 117 / 7739
18
(HPO:0010836) Abnormality of copper homeostasis 27103860 IBIS 2 / 7739
19
(HPO:0010837) Decreased serum ceruloplasmin Frequent [IBIS] 84% (n=12) 27103860 IBIS 2 / 7739
20
(HPO:0010838) High nonceruloplasmin-bound serum copper 27103860 IBIS 1 / 7739
21
(HPO:0010839) Increased urinary copper concentration Very frequent [IBIS] 100% (n=12) 27103860 IBIS 1 / 7739
22
(HPO:0003201) Rhabdomyolysis 27103860 IBIS 27 / 7739
23
(HPO:0001324) Muscle weakness Occasional [IBIS] 8% (n=12) 27103860 IBIS 859 / 7739
24
(HPO:0002459) Dysautonomia 27103860 IBIS 34 / 7739
25
(HPO:0002200) Pseudobulbar signs 27103860 IBIS 15 / 7739
26
(HPO:0003401) Paresthesia Occasional [IBIS] 8% (n=12) 27103860 IBIS 42 / 7739
27
(HPO:0009830) Peripheral neuropathy 16216950 IBIS 206 / 7739
28
(HPO:0007327) Mixed demyelinating and axonal polyneuropathy 16216950 IBIS 1 / 7739
29
(HPO:0001271) Polyneuropathy 16216950 IBIS 56 / 7739
30
(HPO:0001251) Ataxia Occasional [IBIS] 17% (n=12) 27103860 IBIS 413 / 7739
31
(HPO:0002067) Bradykinesia 27103860 IBIS 62 / 7739
32
(HPO:0002321) Vertigo Occasional [IBIS] 17% (n=12) 27103860 IBIS 58 / 7739
33
(HPO:0002275) Poor motor coordination 24798599 IBIS 6 / 7739
34
(HPO:0002071) Abnormality of extrapyramidal motor function 25906525 IBIS 76 / 7739
35
(HPO:0001332) Dystonia Occasional [IBIS] 25% (n=12) 27103860 IBIS 197 / 7739
36
(HPO:0001575) Mood changes 26692151 IBIS 7 / 7739
37
(HPO:0001260) Dysarthria 27103860 IBIS 329 / 7739
38
(HPO:0011999) Paranoia 26692151 IBIS 6 / 7739
39
(HPO:0000726) Dementia 25906525 IBIS 131 / 7739
40
(HPO:0000716) Depression 26692151 IBIS 99 / 7739
41
(HPO:0002307) Drooling 26209285 IBIS 43 / 7739
42
(HPO:0001259) Coma 7322363 IBIS 65 / 7739
43
(HPO:0000751) Personality changes 26692151 IBIS 33 / 7739
44
(HPO:0001959) Polydipsia 23087754 IBIS 43 / 7739
45
(HPO:0100753) Schizophrenia 26692151 IBIS 20 / 7739
46
(HPO:0012452) Restless legs 26940540 IBIS 2 / 7739
47
(HPO:0100022) Abnormality of movement 27103860 IBIS 129 / 7739
48
(HPO:0001288) Gait disturbance 27103860 IBIS 318 / 7739
49
(HPO:0001337) Tremor Frequent [IBIS] 58% (n=12) 27103860 IBIS 200 / 7739
50
(HPO:0002015) Dysphagia 27103860 IBIS 301 / 7739
51
(HPO:0002315) Headache Frequent [IBIS] 58% (n=12) 27103860 IBIS 175 / 7739
52
(HPO:0003259) Elevated serum creatinine Rare [IBIS] 4% (n=25) 18661763 IBIS 31 / 7739
53
(HPO:0003138) Increased blood urea nitrogen Rare [IBIS] 4% (n=25) 18661763 IBIS 14 / 7739
54
(HPO:0003418) Back pain 857745 IBIS 17 / 7739
55
(HPO:0006462) Generalized bone demineralization Frequent [IBIS] 66% (n=32) 857745 IBIS 11 / 7739
56
(HPO:0002749) Osteomalacia 3975658 IBIS 24 / 7739
57
(HPO:0000939) Osteoporosis Frequent [IBIS] 66% (n=32) 857745 IBIS 129 / 7739
58
(HPO:0002748) Rickets 3975658 IBIS 41 / 7739
59
(HPO:0001369) Arthritis 22286624 IBIS 44 / 7739
60
(HPO:0001382) Joint hypermobility Occasional [IBIS] 28% (n=32) 857745 IBIS 231 / 7739
61
(HPO:0001387) Joint stiffness 857745 IBIS 322 / 7739
62
(HPO:0002758) Osteoarthritis Occasional [IBIS] 25% (n=32) 857745 IBIS 78 / 7739
63
(HPO:0001367) Abnormal joint morphology 23576656 IBIS 53 / 7739
64
(HPO:0010886) Osteochondritis Dissecans 857745 IBIS 9 / 7739
65
(HPO:0002653) Bone pain 857745 IBIS 75 / 7739
66
(HPO:0002040) Esophageal varix 4190630 IBIS 23 / 7739
67
(HPO:0001392) Abnormality of the liver 26692151 IBIS 28 / 7739
68
(HPO:0005264) Abnormality of the gallbladder 22286624 IBIS 14 / 7739
69
(HPO:0000952) Jaundice Frequent [IBIS] 42% (n=12) 27103860 IBIS 105 / 7739
70
(HPO:0001394) Cirrhosis 26692151 IBIS 102 / 7739
71
(HPO:0001410) Decreased liver function Very frequent [IBIS] 92% (n=12) 27103860 IBIS 59 / 7739
72
(HPO:0001399) Hepatic failure 25380954 IBIS 80 / 7739
73
(HPO:0004448) Fulminant hepatic failure 26692151 IBIS 4 / 7739
74
(HPO:0004787) Fulminant hepatitis Occasional [IBIS] 17% (n=12) 27103860 IBIS 3 / 7739
75
(HPO:0002240) Hepatomegaly 26288636 IBIS 467 / 7739
76
(HPO:0001971) Hypersplenism 25910248 IBIS 8 / 7739
77
(HPO:0001744) Splenomegaly 25910248 IBIS 337 / 7739
78
(HPO:0000298) Mask-like facies 27103860 IBIS 44 / 7739
79
(HPO:0003781) Excessive salivation Frequent [IBIS] 26209285 IBIS 15 / 7739
80
(HPO:0000707) Abnormality of the nervous system Occasional [IBIS] 27103860 IBIS 61 / 7739
81
(HPO:0000829) Hypoparathyroidism 26692151 IBIS 22 / 7739
82
(HPO:0004334) Dermal atrophy 25617204 IBIS 34 / 7739
83
(HPO:0000980) Pallor Frequent [IBIS] 33% (n=12) 27103860 IBIS 52 / 7739
84
(HPO:0012574) Mesangial proliferation Rare [IBIS] 4% (n=25) 18661763 IBIS 1 / 7739
85
(HPO:0000105) Enlarged kidneys Occasional [IBIS] 12% (n=25) 18661763 IBIS 30 / 7739
86
(HPO:0000121) Nephrocalcinosis 23087754 IBIS 57 / 7739
87
(HPO:0000787) Nephrolithiasis 25120295 IBIS 78 / 7739
88
(HPO:0011038) Abnormality of renal resorption 25120295 IBIS 6 / 7739
89
(HPO:0000790) Hematuria Frequent [IBIS] 56% (n=25) 18661763 IBIS 106 / 7739
90
(HPO:0000083) Renal insufficiency Occasional [IBIS] 28% (n=25) 18661763 IBIS 232 / 7739
91
(HPO:0000124) Renal tubular dysfunction 25120295 IBIS 46 / 7739
92
(HPO:0000093) Proteinuria Frequent [IBIS] 48% (n=25) 18661763 IBIS 169 / 7739
93
(HPO:0003109) Hyperphosphaturia 857745 IBIS 18 / 7739
94
(HPO:0012751) Abnormal basal ganglia MRI signal intensity Occasional [IBIS] 8% (n=12) 27103860 IBIS 4 / 7739
95
(HPO:0012676) Copper accumulation in brain 27103860 IBIS 1 / 7739
96
(MedDRA:10004501) Beta 2 microglobulin urine increased Occasional [IBIS] 24% (n=25) 18661763 IBIS 1 / 7739
97
(MedDRA:10004511) Beta-N-acetyl-D-glucosaminidase increased Occasional [IBIS] 20% (n=25) 18661763 IBIS 1 / 7739
98
(MedDRA:10010075) Coma hepatic 7322363 IBIS 1 / 7739
99
(MedDRA:10036030) Polyarthritis Occasional [IBIS] 16% (n=32) 857745 IBIS 3 / 7739
100
(MedDRA:10038182) Red blood cells urine positive Occasional [IBIS] 28% (n=25) 18661763 IBIS 1 / 7739
101
(OMIM) High liver copper 27103860 IBIS 1 / 7739
102
(OMIM) High urinary copper 27103860 IBIS 1 / 7739
103
(OMIM) Hypokalemic muscle weakness 27103860 IBIS 2 / 7739
104
(OMIM) Labile mood 26692151 IBIS 2 / 7739
105
(OMIM) Low serum ceruloplasmin 27103860 IBIS 1 / 7739
106
(OMIM) Sensorimotor polyneuropathy 16216950 IBIS 2 / 7739

Associated genes:

ATP7B;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Wilson disease is an autosomal recessive disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neurologic abnormalities.

De Bie et al. (2007) provided a detailed review of the molecular pathogenesis of Wilson ...

Diagnosis OMIM Chowrimootoo et al. (1998) investigated the neonatal diagnosis of Wilson disease by measuring ceruloplasmin isoforms in neonatal cord blood samples and venous blood from both healthy adults and patients with Wilson disease. Total ceruloplasmin levels were reduced in ...
Clinical Description OMIM In Wilson disease, the basal ganglia and liver undergo changes that express themselves in neurologic manifestations and signs of cirrhosis, respectively. A disturbance in copper metabolism is somehow involved in the mechanism. Low ceruloplasmin (117700) is found in ...
Genotype-Phenotype Correlations OMIM Gromadzka et al. (2005) studied 142 Polish patients with Wilson disease and identified 26 mutations in the ATP7B gene: 11 truncating, 14 missense, and 1 splice site mutation. Patients with 1 or 2 truncating mutations on their alleles ...
Molecular genetics OMIM Bull et al. (1993) identified 2 patients with Wilson disease who were homozygous for a 7-bp deletion within the coding region of the ATP7B gene (606882.0001). Tanzi et al. (1993) identified 4 mutations in the ATP7B gene in ...
Population genetics OMIM Whereas the worldwide prevalence of Wilson disease is estimated to be on the order of 30 per 1 million, with a gene frequency of 0.56% and a carrier frequency of 1 in 90, a higher prevalence seems to ...
Diagnosis GeneReviews Diagnosis of Wilson disease cannot be made by a single test alone and a combination of tests is always needed as outlined in detail in the AASLD guidelines [Roberts & Schilsky 2008]. ...
Clinical Description GeneReviews Wilson disease can manifest as hepatic, neurologic, hematologic, or psychiatric disturbances, or a combination of these, in individuals ranging in age from three years to over 60 years. Phenotypic expression varies even within families. The phenotypic spectrum has further expanded through molecular genetic testing, which has confirmed the diagnosis in individuals with atypical clinical and biochemical findings [Dening & Berrios 1989, Walshe 1989, Steindl et al 1997, Cox & Roberts 2006, Ala et al 2007]....
Genotype-Phenotype Correlations GeneReviews Mutations that completely prevent function of the gene may tend to produce a more severe phenotype than certain types of missense mutation [Cox 1996, Deguti et al 2004, Liu et al 2004, Panagiotakaki et al 2004]. ...
Differential Diagnosis GeneReviews Other liver diseases presenting with abnormal liver biochemistries with or without hepatomegaly that need to be considered include the following:...
Management GeneReviews To establish the extent of disease and needs in an individual diagnosed with Wilson disease, 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....