EPP
MCID: PRT103
MIFTS: 48

Protoporphyria, Erythropoietic, Autosomal Recessive (EPP) malady

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Skin diseases, Metabolic diseases

Aliases & Classifications for Protoporphyria, Erythropoietic, Autosomal Recessive

Aliases & Descriptions for Protoporphyria, Erythropoietic, Autosomal Recessive:

Name: Protoporphyria, Erythropoietic, Autosomal Recessive 54 13
Erythropoietic Protoporphyria 12 71 50 66 29 14 69
Epp 12 50 56 66
Ferrochelatase Deficiency 50 66 69
Protoporphyria 12 71 50
Erythropoietic Protoporphyria, Autosomal Recessive 23 24
Protoporphyria, Erythropoietic 54 42
Heme Synthetase Deficiency 50 66
Autosomal Erythropoietic Protoporphyria 56
Erythrohepatic Protoporphyria 50
Protoporphyria Erythropoietic 52
Ferrochelatase 13

Characteristics:

Orphanet epidemiological data:

56
autosomal erythropoietic protoporphyria
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Europe),1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

GeneReviews:

23
protoporphyria, erythropoietic, autosomal recessive:
Inheritance autosomal recessive inheritance autosomal dominant inheritance
Onset and clinical course childhood onset


GeneReviews:

23
Penetrance Epp appears to be 100% penetrant when there are biallelic fech loss-of-function variants or compound heterozygosity for a fech loss-of-function variant and a variant that causes low expression of the other fech allele...

Classifications:



External Ids:

OMIM 54 177000
Disease Ontology 12 DOID:13270
ICD10 33 E80.0
MeSH 42 D046351
NCIt 47 C84698
SNOMED-CT 64 51022005
Orphanet 56 ORPHA79278
ICD10 via Orphanet 34 E80.0
MESH via Orphanet 43 D046351
UMLS via Orphanet 70 C0162568
UMLS 69 C0162568

Summaries for Protoporphyria, Erythropoietic, Autosomal Recessive

NIH Rare Diseases : 50 erythropoietic protoporphyria is a type of porphyria. porphyrias are caused by an abnormality in the heme production process. heme is essential in enabling our blood cells to carry oxygen and in breaking down chemical compounds in the liver. erythropoietic protoporphyria is caused by impaired activity of ferrocheletase (fech), an important enzyme in heme production. this results in the build-up of protoporphyrin in the bone marrow, red blood cells, blood plasma, skin, and eventually liver. build up of protoporphyrin can cause extreme sensitivity to sunlight, liver damage, abdominal pain, gallstones, and enlargement of the spleen. last updated: 6/23/2015

MalaCards based summary : Protoporphyria, Erythropoietic, Autosomal Recessive, also known as erythropoietic protoporphyria, is related to protoporphyria, erythropoietic, x-linked and x-linked protoporphyria, and has symptoms including pruritus, edema and decreased liver function. An important gene associated with Protoporphyria, Erythropoietic, Autosomal Recessive is FECH (Ferrochelatase), and among its related pathways/superpathways are Metabolism and Porphyrin and chlorophyll metabolism. The drugs Colestipol and alpha-MSH have been mentioned in the context of this disorder. Affiliated tissues include skin, liver and bone, and related phenotype is integument.

Disease Ontology : 12 An acute porphyria characterized by a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the tissue.

OMIM : 54 Erythropoietic protoporphyria is an inborn error of porphyrin metabolism caused by decreased activity of the enzyme... (177000) more...

UniProtKB/Swiss-Prot : 66 Erythropoietic protoporphyria: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals.

Wikipedia : 71 Ferrochelatase (or protoporphyrin ferrochelatase) is an enzyme that is encoded by the FECH gene in... more...

GeneReviews: NBK100826

Related Diseases for Protoporphyria, Erythropoietic, Autosomal Recessive

Graphical network of the top 20 diseases related to Protoporphyria, Erythropoietic, Autosomal Recessive:



Diseases related to Protoporphyria, Erythropoietic, Autosomal Recessive

Symptoms & Phenotypes for Protoporphyria, Erythropoietic, Autosomal Recessive

Symptoms by clinical synopsis from OMIM:

177000

Clinical features from OMIM:

177000

Human phenotypes related to Protoporphyria, Erythropoietic, Autosomal Recessive:

56 32 (show all 13)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pruritus 56 32 Very frequent (99-80%) HP:0000989
2 edema 56 32 Occasional (29-5%) HP:0000969
3 decreased liver function 56 32 Occasional (29-5%) HP:0001410
4 cirrhosis 56 32 Occasional (29-5%) HP:0001394
5 cholelithiasis 56 32 Occasional (29-5%) HP:0001081
6 microcytic anemia 56 32 Occasional (29-5%) HP:0001935
7 erythema 56 32 Very frequent (99-80%) HP:0010783
8 eczema 56 32 Occasional (29-5%) HP:0000964
9 cutaneous photosensitivity 56 32 Very frequent (99-80%) HP:0000992
10 abnormality of the heme biosynthetic pathway 56 32 Very frequent (99-80%) HP:0010472
11 hypertriglyceridemia 32 HP:0002155
12 hemolytic anemia 32 HP:0001878
13 hepatic failure 32 HP:0001399

UMLS symptoms related to Protoporphyria, Erythropoietic, Autosomal Recessive:


edema, pruritus, burning sensation

MGI Mouse Phenotypes related to Protoporphyria, Erythropoietic, Autosomal Recessive:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 9.02 ALAS2 FECH MC1R PCBD1 UROS

Drugs & Therapeutics for Protoporphyria, Erythropoietic, Autosomal Recessive

Drugs for Protoporphyria, Erythropoietic, Autosomal Recessive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 24)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Colestipol Approved Phase 2, Phase 3 26658-42-4, 50925-79-6 62816
2 alpha-MSH Phase 3,Phase 2
3 Hormone Antagonists Phase 3,Phase 2
4 Hormones Phase 3,Phase 2
5 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 3,Phase 2
6 Hypolipidemic Agents Phase 2, Phase 3
7 Lipid Regulating Agents Phase 2, Phase 3
8 Antimetabolites Phase 2, Phase 3
9 cysteine Nutraceutical Phase 3
10
Iron Approved 7439-89-6 23925
11
Aminolevulinic acid Approved 106-60-5 137
12
Isoniazid Approved 54-85-3 3767
13
Protoporphyrin IX Experimental 553-12-8
14
Canthaxanthin 514-78-3 5281227
15 Protective Agents
16 Antioxidants
17 Trace Elements
18 Micronutrients
19 Dermatologic Agents
20 Anti-Bacterial Agents
21 Photosensitizing Agents
22 Anti-Infective Agents
23 Antitubercular Agents
24 Iron Supplement Nutraceutical

Interventional clinical trials:

(show all 13)
id Name Status NCT ID Phase
1 Phase III Confirmatory Study in Erythropoietic Protoporphyria Unknown status NCT01605136 Phase 3
2 Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP) Completed NCT00979745 Phase 3
3 Phase III Study of L-Cysteine in Patients With Erythropoietic Protoporphyria Completed NCT00004940 Phase 3
4 Sorbent Therapy of the Cutaneous Porphyrias Completed NCT01422915 Phase 2, Phase 3
5 Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP) Completed NCT01097044 Phase 2
6 Does Exercise and Heat Increase the Lightsensibility in Patients With Erythropoietic Protoporphyria Unknown status NCT00206869
7 Study of Cysteine Hydrochloride for Erythropoietic Protoporphyria Completed NCT00004831
8 Canthaxanthin Retinopathy: A Long-term Observation Completed NCT01128062
9 Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact Recruiting NCT01688895
10 Oral Iron for Erythropoietic Protoporphyrias Recruiting NCT02979249
11 Longitudinal Study of the Porphyrias Recruiting NCT01561157
12 Mitoferrin-1 Expression in Erythropoietic Protoporphyria (Porphyria Rare Disease Clinical Research Consortium (RDCRC)) Active, not recruiting NCT01880983
13 Effect of Isoniazid on Protoporphyrin Levels in Erythropoietic Protoporphyria Terminated NCT01550705

Search NIH Clinical Center for Protoporphyria, Erythropoietic, Autosomal Recessive

Cochrane evidence based reviews: protoporphyria, erythropoietic

Genetic Tests for Protoporphyria, Erythropoietic, Autosomal Recessive

Genetic tests related to Protoporphyria, Erythropoietic, Autosomal Recessive:

id Genetic test Affiliating Genes
1 Erythropoietic Protoporphyria 29
2 Erythropoietic Protoporphyria, Autosomal Recessive 24 FECH

Anatomical Context for Protoporphyria, Erythropoietic, Autosomal Recessive

MalaCards organs/tissues related to Protoporphyria, Erythropoietic, Autosomal Recessive:

39
Skin, Liver, Bone, Bone Marrow, Spleen

Publications for Protoporphyria, Erythropoietic, Autosomal Recessive

Variations for Protoporphyria, Erythropoietic, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Protoporphyria, Erythropoietic, Autosomal Recessive:

66 (show all 23)
id Symbol AA change Variation ID SNP ID
1 FECH p.Gly55Cys VAR_002383 rs3848519
2 FECH p.Ile186Thr VAR_002384
3 FECH p.Met267Ile VAR_002385 rs118204037
4 FECH p.His386Pro VAR_002386
5 FECH p.Phe417Ser VAR_002387 rs118204039
6 FECH p.Pro62Arg VAR_030553 rs150830931
7 FECH p.Ile71Lys VAR_030554
8 FECH p.Gln139Leu VAR_030555
9 FECH p.Ser151Pro VAR_030556
10 FECH p.Glu178Lys VAR_030557
11 FECH p.Leu182Arg VAR_030558
12 FECH p.Tyr191His VAR_030559
13 FECH p.Pro192Thr VAR_030560
14 FECH p.Cys236Tyr VAR_030561 rs761962617
15 FECH p.Phe260Leu VAR_030562
16 FECH p.Thr283Ile VAR_030563
17 FECH p.Met288Lys VAR_030564
18 FECH p.Pro334Leu VAR_030565 rs150146721
19 FECH p.Val362Gly VAR_030566 rs118204040
20 FECH p.Lys379Asn VAR_030567
21 FECH p.Cys406Ser VAR_030568
22 FECH p.Cys406Tyr VAR_030569
23 FECH p.Ser264Leu VAR_054629

ClinVar genetic disease variations for Protoporphyria, Erythropoietic, Autosomal Recessive:

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 FECH NM_001012515.2(FECH): c.1268T> C (p.Phe423Ser) single nucleotide variant Pathogenic rs118204039 GRCh37 Chromosome 18, 55217966: 55217966
2 FECH NM_000140.3(FECH): c.1077+1G> A single nucleotide variant Pathogenic rs786205245 GRCh38 Chromosome 18, 57554259: 57554259
3 FECH NM_000140.3(FECH): c.1137+3A> G single nucleotide variant Pathogenic rs202147607 GRCh37 Chromosome 18, 55218544: 55218544
4 FECH NM_001012515.2(FECH): c.1103T> G (p.Val368Gly) single nucleotide variant Pathogenic rs118204040 GRCh37 Chromosome 18, 55218599: 55218599
5 FECH NM_000140.3(FECH): c.314+2T> G single nucleotide variant Pathogenic rs149067146 GRCh37 Chromosome 18, 55240476: 55240476
6 FECH NM_000140.3(FECH): c.195_314del single nucleotide variant Pathogenic rs786205246 GRCh38 Chromosome 18, 57573240: 57573240
7 FECH NM_000140.3(FECH): c.1078_1137del single nucleotide variant Pathogenic rs879255507 GRCh38 Chromosome 18, 57551317: 57551317
8 FECH NM_001012515.2(FECH): c.1154delA (p.Lys385Argfs) deletion Pathogenic rs764466739 GRCh38 Chromosome 18, 57551316: 57551316
9 FECH NM_000140.3(FECH): c.68_194del single nucleotide variant Pathogenic rs786205247 GRCh38 Chromosome 18, 57580062: 57580062
10 FECH NM_000140.3(FECH): c.580_584delTACAG (p.Tyr194Leufs) deletion Pathogenic rs786205248 GRCh37 Chromosome 18, 55233693: 55233697
11 FECH NM_001012515.2(FECH): c.571G> A (p.Ala191Thr) single nucleotide variant Pathogenic rs397514476 GRCh37 Chromosome 18, 55233724: 55233724
12 FECH NM_000140.3(FECH): c.854A> G (p.Gln285Arg) single nucleotide variant Likely pathogenic rs370708663 GRCh37 Chromosome 18, 55222135: 55222135
13 FECH NM_000140.3(FECH): c.1001C> T (p.Pro334Leu) single nucleotide variant Likely pathogenic rs150146721 GRCh37 Chromosome 18, 55221568: 55221568

Expression for Protoporphyria, Erythropoietic, Autosomal Recessive

Search GEO for disease gene expression data for Protoporphyria, Erythropoietic, Autosomal Recessive.

Pathways for Protoporphyria, Erythropoietic, Autosomal Recessive

GO Terms for Protoporphyria, Erythropoietic, Autosomal Recessive

Cellular components related to Protoporphyria, Erythropoietic, Autosomal Recessive according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.35 ALAS2 CPOX FECH PPOX UROS
2 mitochondrial intermembrane space GO:0005758 9.16 CPOX PPOX
3 mitochondrial inner membrane GO:0005743 8.92 ALAS2 CPOX FECH PPOX

Biological processes related to Protoporphyria, Erythropoietic, Autosomal Recessive according to GeneCards Suite gene sharing:

(show all 14)
id Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.71 ALAD FECH PPOX
2 heme biosynthetic process GO:0006783 9.7 ALAD ALAS2 CPOX FECH HMBS PPOX
3 response to lead ion GO:0010288 9.58 ALAD CPOX FECH
4 tetrapyrrole biosynthetic process GO:0033014 9.56 ALAD ALAS2 HMBS UROS
5 response to arsenic-containing substance GO:0046685 9.54 ALAD CPOX FECH
6 response to metal ion GO:0010038 9.52 ALAD FECH
7 response to iron ion GO:0010039 9.51 ALAD CPOX
8 response to methylmercury GO:0051597 9.5 ALAD CPOX FECH
9 response to inorganic substance GO:0010035 9.49 ALAD CPOX
10 response to insecticide GO:0017085 9.48 CPOX FECH
11 protoporphyrinogen IX metabolic process GO:0046501 9.46 FECH PPOX
12 response to platinum ion GO:0070541 9.43 ALAD FECH
13 porphyrin-containing compound biosynthetic process GO:0006779 9.43 ALAD CPOX FECH HMBS PPOX UROS
14 protoporphyrinogen IX biosynthetic process GO:0006782 9.1 ALAD ALAS2 CPOX HMBS PPOX UROS

Molecular functions related to Protoporphyria, Erythropoietic, Autosomal Recessive according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 lyase activity GO:0016829 8.92 ALAD FECH PCBD1 UROS

Sources for Protoporphyria, Erythropoietic, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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