COLED
MCID: CLD014
MIFTS: 37

Cole Disease (COLED)

Categories: Gastrointestinal diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Cole Disease

MalaCards integrated aliases for Cole Disease:

Name: Cole Disease 57 20 43 58 72 36 29 6 39 70
Guttate Hypopigmentation and Punctate Palmoplantar Keratoderma with or Without Ectopic Calcification 57 43
Coled 57 72
Punctate Palmoplantar Keratoderma with or Without Ectopic Calcification 20
Guttate Hypopigmentation and Punctate Palmoplantar Keratoderma 58
Hypopigmentation and Punctate Keratosis of the Palms and Soles 58
Hypopigmentation-Punctate Palmoplantar Keratoderma Syndrome 58
Albinoidism, Oculocutaneous, Autosomal Dominant 70
Hypopigmentation Disorder 70
Guttate Hypopigmentation 20
Hypopigmentation 44
Col 73

Characteristics:

Orphanet epidemiological data:

58
hypopigmentation-punctate palmoplantar keratoderma syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
skin lesions manifest in the first year of life
hair, teeth, and nails are normal


HPO:

31
cole disease:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare skin diseases


External Ids:

OMIM® 57 615522
KEGG 36 H01394
ICD10 via Orphanet 33 Q82.8
Orphanet 58 ORPHA324561
UMLS 70 C0162835 C1876214 C3809781

Summaries for Cole Disease

OMIM® : 57 Cole disease is a rare autosomal dominant disorder characterized by congenital or early-onset punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show nonspecific changes including hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer (summary by Eytan et al., 2013). Some patients also exhibit calcinosis cutis or early-onset calcific tendinopathy (Eytan et al., 2013). (615522) (Updated 05-Apr-2021)

MalaCards based summary : Cole Disease, also known as guttate hypopigmentation and punctate palmoplantar keratoderma with or without ectopic calcification, is related to oculocerebral syndrome with hypopigmentation and yemenite deaf-blind hypopigmentation syndrome, and has symptoms including achromia of skin An important gene associated with Cole Disease is ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1), and among its related pathways/superpathways are Purine metabolism and Starch and sucrose metabolism. The drugs Fluorouracil and Immunosuppressive Agents have been mentioned in the context of this disorder. Affiliated tissues include skin, and related phenotypes are hyperkeratosis and palmoplantar keratoderma

MedlinePlus Genetics : 43 Cole disease is a disorder that affects the skin. People with this disorder have areas of unusually light-colored skin (hypopigmentation), typically on the arms and legs, and spots of thickened skin on the palms of the hands and the soles of the feet (punctate palmoplantar keratoderma). These skin features are present at birth or develop in the first year of life.In some cases, individuals with Cole disease develop abnormal accumulations of the mineral calcium (calcifications) in the tendons, which can cause pain during movement. Calcifications may also occur in the skin or breast tissue.

KEGG : 36 Cole disease is a rare autosomal-dominant disorder characterized by congenital or early-onset punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs, but not the trunk or acral regions. Mutations in ENPP1, encoding ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), are associated with Cole disease. ENPP1 catalyzes the hydrolysis of ATP to AMP and generates extracellular inorganic pyrophosphate.

UniProtKB/Swiss-Prot : 72 Cole disease: A rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy.

Related Diseases for Cole Disease

Diseases related to Cole Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 337)
# Related Disease Score Top Affiliating Genes
1 oculocerebral syndrome with hypopigmentation 11.6
2 yemenite deaf-blind hypopigmentation syndrome 11.6
3 tietz albinism-deafness syndrome 11.5
4 vici syndrome 11.5
5 hyperpigmentation with or without hypopigmentation, familial progressive 11.5
6 griscelli syndrome 11.5
7 hypopigmentation, organomegaly, and delayed myelination and development 11.4
8 osteoporosis and oculocutaneous hypopigmentation syndrome 11.4
9 waardenburg syndrome, type 2e 11.3
10 griscelli syndrome, type 2 11.3
11 griscelli syndrome, type 1 11.2
12 oculocerebral hypopigmentation syndrome of preus 11.2
13 hypopigmentation of the skin 11.2
14 aland island eye disease 11.2
15 dilution, pigmentary 11.0
16 hypomelanotic disorder 11.0
17 hypopigmentation of eyelid 11.0
18 hypomelanosis of ito 11.0
19 griscelli syndrome, type 3 11.0
20 epidermolysis bullosa simplex with mottled pigmentation 11.0
21 albinism, ocular, type i 11.0
22 reticulate acropigmentation of kitamura 11.0
23 ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies 11.0
24 oculocutaneous albinism, type viii 11.0
25 raindrop hypopigmentation 10.9
26 chediak-higashi syndrome 10.9
27 genetic hypopigmentation of the skin 10.9
28 linear hypopigmentation and craniofacial asymmetry with acral, ocular and brain anomalies 10.9
29 acrocephalopolydactylous dysplasia 10.8
30 menkes disease 10.8
31 ocular albinism, x-linked 10.8
32 dyschromatosis universalis hereditaria 1 10.8
33 waardenburg syndrome, type 3 10.8
34 macular dystrophy, concentric annular 10.8
35 vitreoretinochoroidopathy 10.8
36 gillespie syndrome 10.8
37 bloom syndrome 10.8
38 fanconi anemia, complementation group a 10.8
39 cartilage-hair hypoplasia 10.8
40 revesz syndrome 10.8
41 mismatch repair cancer syndrome 1 10.8
42 albinism-deafness syndrome 10.8
43 incontinentia pigmenti 10.8
44 poikiloderma with neutropenia 10.8
45 albinism, oculocutaneous, type ib 10.8
46 hyperpigmentation, familial progressive, 1 10.8
47 epidermolysis bullosa simplex, generalized, with scarring and hair loss 10.8
48 vitiligo-associated multiple autoimmune disease susceptibility 6 10.5
49 vitiligo-associated multiple autoimmune disease susceptibility 1 10.5
50 dowling-degos disease 1 10.4

Graphical network of the top 20 diseases related to Cole Disease:



Diseases related to Cole Disease

Symptoms & Phenotypes for Cole Disease

Human phenotypes related to Cole Disease:

31
# Description HPO Frequency HPO Source Accession
1 hyperkeratosis 31 HP:0000962
2 palmoplantar keratoderma 31 HP:0000982
3 epidermal acanthosis 31 HP:0025092
4 hypergranulosis 31 HP:0025114

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skin Nails Hair Skin Histology:
hyperkeratosis
hypergranulosis
acanthosis
hyperorthokeratosis
normal number of melanocytes
more
Skin Nails Hair Nails:
normal nails

Chest Breasts:
microcalcifications on mammography (in some patients)

Skeletal Pelvis:
calcific tendinopathy of hips (in some patients)

Skeletal Feet:
calcific tendinopathy of heels (in some patients)

Skin Nails Hair Skin Electron Microscopy:
increased melanosomes in cytoplasm and dendrites of melanocytes
paucity of melanosomes in keratinocytes

Skin Nails Hair Hair:
normal hair

Head And Neck Mouth:
normal teeth

Abdomen Spleen:
splenic calcification (in some patients)

Skeletal Limbs:
calcific tendinopathy of shoulders (in some patients)
calcific tendinopathy of wrists (in some patients)

Skin Nails Hair Skin:
hypopigmented macules, primarily on extremities
punctate palmoplantar keratoderma

Muscle Soft Tissue:
calcific tendinopathy, early-onset (in some patients)

Clinical features from OMIM®:

615522 (Updated 05-Apr-2021)

UMLS symptoms related to Cole Disease:


achromia of skin

Drugs & Therapeutics for Cole Disease

Drugs for Cole Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Fluorouracil Approved Phase 4 51-21-8 3385
2 Immunosuppressive Agents Phase 4
3 Immunologic Factors Phase 4
4 Antimetabolites Phase 4
5
Chlorhexidine Approved, Vet_approved 55-56-1 2713 9552079
6
Lidocaine Approved, Vet_approved 137-58-6 3676
7 Chlorhexidine gluconate
8 Anesthetics
9 Ulipristal acetate 126784-99-4
10 Pharmaceutical Solutions
11 Hemostatics

Interventional clinical trials:

(show all 15)
# Name Status NCT ID Phase Drugs
1 Conventional Microneedling Compared to Microneedling Associated With 5-FU Infusion (Microinfusion of Medication Into the Skin - MMP) for Idiopathic Guttate Hypomelanosis (IGH) Repigmentation Recruiting NCT02904564 Phase 4 MMP with 5-FU;MMP with Saline infusion
2 Efficacy of810 nm Diode Laser on Gingival Pigmentation Completed NCT02143375 Phase 1
3 A Proof of Concept Cases Series on the Use of the Epidermal Expansion System to Harvest and Place Suction Blister Epidermal Grafts on Hypopigmented Skin and Surgical Wounds Unknown status NCT01590329
4 Microneedling for Acquired Hypomelanosis : A Randomized Controlled Trial Completed NCT04419350
5 A Single-Center Prospective, Open-Label Study of the Excel V 532 nm KTP Laser for the Treatment of Poikiloderma of Civatte Completed NCT01491620
6 The Effect of Jazz on Postoperative Pain and Stress in Patients Undergoing Elective Hysterectomy Completed NCT01834027
7 "Underwater" Technique With Submucosal Solution of Viscose Solution -SIC 8000 (EleviewTM) - For Endoscopic Resection of Cole-rectal Polyps With Signs of Fibrosis. Pilot Study Completed NCT03756636
8 Comparison Between Ultrasonography and Cole Formula in Predicting Uncuffed Endotracheal Tube Diameter Completed NCT02754531
9 Effectiveness of Ultrasonography and The Cole Formula on the Evaluation of the Appropriate Endotracheal Tube Size Completed NCT03280498
10 Gingival Depigmentation With Er,Cr:YSGG and Diode Laser: Randomized Clinical Trial to Evaluate the Repigmentation and Patient Perceptions Completed NCT04680806
11 Excimer Light Treatment for Idiopathic Guttate Hypomelanosis: A Pilot Study Completed NCT01956435
12 Clinical Comparison of the Effect of Non-eugenol Containing Periodontal Pack With and Without Platelet Rich Fibrin on Post-operative Pain and Wound Healing After Surgical Gingival Depigmentation: A Randomized Clinical Trial Recruiting NCT04495205 Early Phase 1
13 A Comparative Evaluation of Various Patient Centered Outcomes Following Gingival Depigmentation Using Diode LASER in Different Modes: A Randomized Clinical Trial Enrolling by invitation NCT04217434
14 Hypo-pigmented Skin Lesions in Children : Dermoscopic Evaluation Not yet recruiting NCT04089475
15 In Vivo Imaging of Pigmentary Disorders by Reflectance Confocal Microscopy Terminated NCT00771355

Search NIH Clinical Center for Cole Disease

Inferred drug relations via UMLS 70 / NDF-RT 51 :


Dihydroxyacetone

Cochrane evidence based reviews: hypopigmentation

Genetic Tests for Cole Disease

Genetic tests related to Cole Disease:

# Genetic test Affiliating Genes
1 Cole Disease 29 ENPP1

Anatomical Context for Cole Disease

MalaCards organs/tissues related to Cole Disease:

40
Skin

Publications for Cole Disease

Articles related to Cole Disease:

(show all 15)
# Title Authors PMID Year
1
Cole Disease Results from Mutations in ENPP1. 61 57 6
24075184 2013
2
Cole disease: guttate hypopigmentation and punctate palmoplantar keratoderma. 61 6 57
19380683 2009
3
Hypopigmentation with punctate keratosis of the palms and soles. 57
132904 1976
4
A novel ENPP1 mutation identified in a multigenerational family affected by Cole disease. 61
32598042 2020
5
Development of a Tailored Behavioral Weight Loss Program for Veterans With PTSD (MOVE!+UP): A Mixed-Methods Uncontrolled Iterative Pilot Study. 61
32162528 2020
6
Novel homozygous ENPP1 mutation causes generalized arterial calcifications of infancy, thrombocytopenia, and cardiovascular and central nervous system syndrome. 61
31444901 2019
7
Costs of an ostomy self-management training program for cancer survivors. 61
29139176 2018
8
ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis. 61
28964717 2018
9
Association of Cole disease with novel heterozygous mutations in the somatomedin-B domains of the ENPP1 gene: necessary, but not always sufficient. 61
26617416 2016
10
Cole disease: a case report and literature review. 61
25065726 2015
11
Effects of light emitting diode (LED) therapy at 940 nm on inflammatory root resorption in rats. 61
22350492 2013
12
Palmoplantar hyperkeratoses and hypopigmentation. Cole disease. 61
21597676 2011
13
Cole disease: hypopigmentation with punctate keratosis of the palms and soles. 61
12220272 2002
14
[Effect of excess cooling on rat liver mitochondria: release of K+ and malate dehydrogenase at lipid phase transition temperatures]. 61
7082692 1982
15
[Congenital dyskeratosis with atresia of the lacrimal points: Zinsser-Engman-Cole disease]. 61
13445372 1957

Variations for Cole Disease

ClinVar genetic disease variations for Cole Disease:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ENPP1 NM_006208.3(ENPP1):c.530G>A (p.Cys177Tyr) SNV Pathogenic 88750 rs397518475 GRCh37: 6:132172381-132172381
GRCh38: 6:131851241-131851241
2 ENPP1 NM_006208.3(ENPP1):c.491G>C (p.Cys164Ser) SNV Pathogenic 88751 rs397518476 GRCh37: 6:132172342-132172342
GRCh38: 6:131851202-131851202
3 ENPP1 NM_006208.3(ENPP1):c.446G>C (p.Cys149Ser) SNV Pathogenic 88752 rs397518477 GRCh37: 6:132172297-132172297
GRCh38: 6:131851157-131851157
4 ENPP1 NM_006208.3(ENPP1):c.1391A>G (p.Asp464Gly) SNV Uncertain significance 982597 GRCh37: 6:132190615-132190615
GRCh38: 6:131869475-131869475

UniProtKB/Swiss-Prot genetic disease variations for Cole Disease:

72
# Symbol AA change Variation ID SNP ID
1 ENPP1 p.Cys149Ser VAR_070782 rs397518477
2 ENPP1 p.Cys164Ser VAR_070783 rs397518476
3 ENPP1 p.Cys177Tyr VAR_070784 rs397518475
4 ENPP1 p.Cys133Arg VAR_077257
5 ENPP1 p.Cys177Ser VAR_077258
6 ENPP1 p.Cys120Arg VAR_081644

Expression for Cole Disease

Search GEO for disease gene expression data for Cole Disease.

Pathways for Cole Disease

Pathways related to Cole Disease according to KEGG:

36
# Name Kegg Source Accession
1 Purine metabolism hsa00230
2 Starch and sucrose metabolism hsa00500
3 Riboflavin metabolism hsa00740
4 Nicotinate and nicotinamide metabolism hsa00760
5 Pantothenate and CoA biosynthesis hsa00770

GO Terms for Cole Disease

Sources for Cole Disease

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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