MCID: OCH001
MIFTS: 38

Ochronosis

Categories: Bone diseases, Rare diseases
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Aliases & Classifications for Ochronosis

MalaCards integrated aliases for Ochronosis:

Name: Ochronosis 11 19 75 53 43 14 71

Classifications:



External Ids:

Disease Ontology 11 DOID:14223
MeSH 43 D009794
NCIt 49 C84938
SNOMED-CT 68 21924005
UMLS 71 C0028817

Summaries for Ochronosis

GARD: 19 Ochronosis is the bluish-black or grey-blue discoloration of the skin, especially the ear cartilage, the ocular (eye) tissue, and other body locations. It can occurs in individuals with alkaptonuria, an inherited metabolic disorder; or because of exposure to various substances. Ochronosis associated with alkaptonuria is caused by a genetic change in the HGD gene, which results in the accumulation and deposition of homogentisic acid (HGA) in cartilage. The affected tissue becomes weak and brittle with time, leading to chronic inflammation, joint pain, and osteoarthritis. Alkaptonuria is inherited in an autosomal recessive manner. Alkaptonuria can be diagnosed based on the symptoms, laboratory testing, and genetic testing. When Ochronosis is due to exposure to substances (called exogenous Ochronosis), the condition is not inherited. Exogenous Ochronosis is associated with malarial drugs, skin-lightening creams and over-exposure to the sun. Other than the skin findings, there are no other health affects. Exogenous Ochronosis may be hard to diagnose.

MalaCards based summary: Ochronosis is related to alkaptonuria and abdominal obesity-metabolic syndrome 1, and has symptoms including muscle weakness, polydipsia and dry skin. An important gene associated with Ochronosis is HGD (Homogentisate 1,2-Dioxygenase), and among its related pathways/superpathways are Metabolism and Regulation of expression of SLITs and ROBOs. The drugs Nitisinone and D-Tyrosine have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and heart, and related phenotype is pigmentation.

Disease Ontology: 11 A connective tissue disease characterized by bluish-brown discoloration of connective tissues that develops from the deposition of homogentisic acid and subsequent oxidation and polymerization reactions.

Wikipedia: 75 Ochronosis is a syndrome caused by the accumulation of homogentisic acid in connective tissues. The... more...

Related Diseases for Ochronosis

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

(show top 50) (show all 167)
# Related Disease Score Top Affiliating Genes
1 alkaptonuria 32.1 TYR HPD HGD FAH
2 abdominal obesity-metabolic syndrome 1 30.0 HGD FAH
3 melanoma in congenital melanocytic nevus 29.4 TYR MITF MC1R
4 tyrosinemia 29.2 TYR HPD HGD FAH
5 exogenous ochronosis 11.6
6 osteoarthritis 10.7
7 arthropathy 10.7
8 aortic valve disease 2 10.5
9 spondyloarthropathy 1 10.3
10 spondylitis 10.3
11 disorder of tyrosine metabolism 10.3
12 aortic valve disease 3 10.3
13 cartilage disease 10.2
14 nephrolithiasis, calcium oxalate 10.2
15 pentosuria 10.2 HPD HGD
16 villonodular synovitis 10.2 NAA50 NAA30
17 neurogenic arthropathy 10.2 NAA50 NAA30
18 spondylosis 10.2
19 back pain 10.2
20 argyria 10.2
21 melanoma, cutaneous malignant 8 10.1 TYR MITF
22 spinal cord melanoma 10.1 TYR MITF
23 uterus perivascular epithelioid cell tumor 10.1 TYR MITF
24 cervix melanoma 10.1 TYR MITF
25 microphthalmia, syndromic 1 10.1 NAA50 NAA30
26 epithelioid cell melanoma 10.1 TYR MITF
27 albinism, ocular, with late-onset sensorineural deafness 10.1 TYR MITF
28 chondrocalcinosis 10.1
29 gout 10.1
30 heart valve disease 10.1
31 inherited metabolic disorder 10.1
32 pigmentation anomaly of the skin 10.1
33 malignant spindle cell melanoma 10.1 TYR MITF
34 waardenburg syndrome, type 4c 10.1 TYR MITF
35 acute contagious conjunctivitis 10.1 TYRP1 TYR
36 acute conjunctivitis 10.1 TYRP1 TYR
37 mucosal melanoma 10.1 TYR MITF
38 waardenburg syndrome, type 2e 10.1 TYR MITF
39 aortic valve disease 1 10.0
40 astigmatism 10.0
41 urolithiasis 10.0
42 ankylosis 10.0
43 aortic valve insufficiency 10.0
44 syndromic microphthalmia 10.0 NAA50 CRYAA
45 pigmentation disease 10.0 TYR MITF
46 waardenburg syndrome, type 1 10.0 TYR MITF
47 lentigines 10.0 TYR MC1R
48 waardenburg syndrome, type 4a 10.0 TYR MITF
49 sarcoidosis 1 9.9
50 hemochromatosis, type 1 9.9

Graphical network of the top 20 diseases related to Ochronosis:



Diseases related to Ochronosis

Symptoms & Phenotypes for Ochronosis

UMLS symptoms related to Ochronosis:


muscle weakness; polydipsia; dry skin

MGI Mouse Phenotypes related to Ochronosis:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 pigmentation MP:0001186 8.92 MC1R MITF TYR TYRP1

Drugs & Therapeutics for Ochronosis

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nitisinone Approved, Investigational Phase 2, Phase 3 104206-65-7 115355
2
D-Tyrosine Approved, Experimental, Investigational, Nutraceutical Phase 2 133585-56-5, 60-18-4, 556-02-5 1153 6057

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 An International, Multicentre, Randomised, Evaluator-blind, No-treatment Controlled, Parallel-group Study to Assess the Efficacy and Safety of Once Daily Nitisinone in Patients With Alkaptonuria After 12 Months of Treatment, Followed by an Additional 36 Month Treatment Period. Unknown status NCT01916382 Phase 3 Nitisinone
2 Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria Completed NCT01390077 Phase 2, Phase 3 Nitisinone
3 Long-Term Clinical Trial of Nitisinone in Alkaptonuria Completed NCT00107783 Phase 2 Nitisinone (NTBC)
4 An International, Multicentre, Randomised, Open-label, No-treatment Controlled, Parallel-group, Dose-response Study to Investigate the Effect of Once Daily Nitisinone on 24-hour Urinary Homogentisic Acid Excretion in Patients With Alkaptonuria After 4 Weeks Treatment. Completed NCT01828463 Phase 2 Nitisinone
5 Clinical, Biochemical, and Molecular Investigations Into Alkaptonuria Recruiting NCT00005909
6 Questionnaire Follow=up Study Sonia 2 Recruiting NCT04510142
7 Determining Individualised Gait Modification Strategies to Reduce Knee Joint Moments in Alkaptonuria Patients Using Real-time Feedback Not yet recruiting NCT04142671

Search NIH Clinical Center for Ochronosis

Cochrane evidence based reviews: ochronosis

Genetic Tests for Ochronosis

Anatomical Context for Ochronosis

Organs/tissues related to Ochronosis:

MalaCards : Skin, Eye, Heart, Bone, Spinal Cord, Kidney, Breast

Publications for Ochronosis

Articles related to Ochronosis:

(show top 50) (show all 786)
# Title Authors PMID Year
1
Aortic stenosis in cardiovascular ochronosis. 53 62
17213354 2007
2
Ochronotic arthropathy: disappearance of alkaptonuria after liver transplantation for hepatitis B-related cirrhosis. 53 62
16371803 2005
3
Use of nitisinone in patients with alkaptonuria. 53 62
15931605 2005
4
Alkaptonuric ochronosis: a case report. 53 62
15727283 2005
5
Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain. 53 62
15529343 2004
6
Alkaptonuria and lumbar disc herniation. Report of three cases. 53 62
12546396 2003
7
Natural history of alkaptonuria. 53 62
12501223 2002
8
Aortic stenosis in endogenous ochronosis. 53 62
10461246 1999
9
Hereditary ochronosis: hyperpigmented skin overlying cartilaginous structures. 53 62
10388955 1999
10
Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene. 53 62
10340975 1999
11
[Alkaptonuria, prostatic calculi, and ectopic ureter]. 53 62
9214216 1997
12
The clinical manifestations of ochronosis: a review. 53 62
8571731 1995
13
Alkaptonuria and renal failure: a case report and review of the literature. 53 62
1495952 1992
14
Minocycline induced discoloration of the aortic intima and valve: A case report. 62
36335620 2022
15
A robust bacterial high-throughput screening system to evaluate single nucleotide polymorphisms of human homogentisate 1,2-dioxygenase in the context of alkaptonuria. 62
36376482 2022
16
Ocular Ochronosis in Alkaptonuria. 62
35773072 2022
17
Disc calcifications: Think of ochronosis. 62
35504514 2022
18
[Ochronosis: A case report]. 62
35659777 2022
19
Descemet's membrane folds in ochronosis: a case report. 62
36183119 2022
20
Exogenous ochronosis successfully treated with the combination of intense pulsed light and fractional CO2 laser. 62
36273949 2022
21
Hyperpigmentation: Looking beyond hydroquinone. 62
35020267 2022
22
Analysis of the Phenotype Differences in Siblings with Alkaptonuria. 62
36295892 2022
23
Sarcoidal granuloma on exogenous ochronosis. 62
35184903 2022
24
Adequacy of nitisinone for the management of alkaptonuria. 62
36045846 2022
25
Endogenous Ochronosis: A Rare Entity. 62
36262587 2022
26
Basophilic, Thickened Collagen Bundles Seen in Late-Stage Exogenous Ochronosis. 62
35234189 2022
27
The Contribution of Imaging Beyond Clinical Diagnosis, the Ochronosis and Synovio-entheseal Complex Examples. 62
36465319 2022
28
Exogenous ochronosis associated with hydroquinone: a systematic review. 62
34486734 2022
29
Total Knee Replacement in Alkaptonuric Ochronosis. 62
35671127 2022
30
Dogliotti and Phillips classifications are unsuitable for grading the histopathological findings of exogenous ochronosis. 62
34918365 2022
31
Blue man: Ochronosis in Otolaryngology. 62
35441025 2022
32
Alkaptonuria in Russia. 62
34504318 2022
33
THE USE OF NEAR INFRARED SPECTROSCOPY IN ALKAPTONURIA - THE MISLEADING OCHRONOSIS - A CASE REPORT AND LITERATURE REVIEW. 62
35334175 2022
34
Neglected alkaptonuric patient presented with low back pain and radiculopathy: A case report. 62
35127215 2022
35
Dermoscopy of acquired pigmentary disorders: a comprehensive review. 62
34235719 2022
36
Incidental diagnosis of ochronosis by aortic valve replacement. 62
35444851 2022
37
Bilateral Breast Ochronosis: a Case Report. 62
34381863 2021
38
Clinical and Surgical Insights on Bilateral Total Knee Arthroplasty in Ochronotic Arthropathy: A Case-based Review. 62
35415137 2021
39
Alkaptonuria: clinical manifestations and an updated approach to treatment of a rare disease. 62
34876442 2021
40
Black cartilage: Incidentally discovered articular ochronosis during arthroplasty. 62
34264534 2021
41
Occupational Localized Cutaneous Argyria With Pseudo-Ochronosis in a Jeweler. 62
33606379 2021
42
Perforating and granulomatous exogenous ochronosis. 62
33470444 2021
43
Ochronotic Surprise during Total Knee Replacement! A Case Report. 62
35415103 2021
44
A novel deep intronic variant strongly associates with Alkaptonuria. 62
34686677 2021
45
Ochronotic heart disease leading to severe aortic valve and coronary artery stenosis. 62
34120368 2021
46
Homogentisic acid induces cytoskeleton and extracellular matrix alteration in alkaptonuric cartilage. 62
33469937 2021
47
Black Aorta from Alkaptonuria. 62
34715699 2021
48
Evaluating the aortic stenosis phenotype before and after the effect of homogentisic acid lowering therapy: Analysis of a large cohort of eighty-one alkaptonuria patients. 62
34059444 2021
49
Exogenous ochronosis associated with dimethoxytolyl propylresorcinol (UP302). 62
34031918 2021
50
Development of an Effective Therapy for Alkaptonuria - Lessons for Osteoarthritis. 62
36465977 2021

Variations for Ochronosis

Expression for Ochronosis

Search GEO for disease gene expression data for Ochronosis.

Pathways for Ochronosis

GO Terms for Ochronosis

Cellular components related to Ochronosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 melanosome membrane GO:0033162 8.92 TYRP1 TYR

Biological processes related to Ochronosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 melanin biosynthetic process GO:0042438 9.73 TYRP1 TYR MC1R
2 melanocyte differentiation GO:0030318 9.67 TYRP1 MITF
3 L-phenylalanine catabolic process GO:0006559 9.63 HPD HGD FAH
4 tyrosine catabolic process GO:0006572 9.43 HPD HGD FAH
5 aromatic amino acid metabolic process GO:0009072 9.32 HPD FAH
6 pigmentation GO:0043473 9.1 TYRP1 TYR MITF MC1R

Molecular functions related to Ochronosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.55 TYRP1 TYR HPD HGD
2 acetyltransferase activity GO:0016407 9.26 NAA50 NAA30
3 peptide alpha-N-acetyltransferase activity GO:0004596 9.26 NAA50 NAA30
4 tyrosinase activity GO:0004503 8.92 TYRP1 TYR

Sources for Ochronosis

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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