XLEPP
MCID: PRT094
MIFTS: 31

Protoporphyria, Erythropoietic, X-Linked (XLEPP)

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

Aliases & Classifications for Protoporphyria, Erythropoietic, X-Linked

MalaCards integrated aliases for Protoporphyria, Erythropoietic, X-Linked:

Name: Protoporphyria, Erythropoietic, X-Linked 56 29 13 6 39
Protoporphyria, Erythropoietic, X-Linked Dominant 56 71
X-Linked Erythropoietic Protoporphyria 58 17
Xldpp 56 58
Protoporphyria, Erythropoietic, X-Linked Dominant; Xldpp 56
Erythropoietic Protoporphyria, X-Linked Dominant 73
X-Linked Dominant Erythropoietic Protoporphyria 58
Erythrohepatic Protoporphyria, X-Linked 56
X-Linked Dominant Protoporphyria 58
Xlepp 56
Xldpt 73
Xlpp 58
Xlp 58

Characteristics:

Orphanet epidemiological data:

58
x-linked erythropoietic protoporphyria
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

56
Miscellaneous:
onset in early childhood
some females with the mutation may be unaffected or mildly affected due to skewed x-chromosome inactivation

Inheritance:
x-linked


HPO:

31
protoporphyria, erythropoietic, x-linked:
Onset and clinical course childhood onset
Inheritance x-linked dominant inheritance


Classifications:

Orphanet: 58  
Rare hepatic diseases
Rare renal diseases
Rare skin diseases
Inborn errors of metabolism


External Ids:

OMIM 56 300752
OMIM Phenotypic Series 56 PS177000
MeSH 43 D046351
ICD10 via Orphanet 33 E80.0
UMLS via Orphanet 72 C2677889
Orphanet 58 ORPHA443197
MedGen 41 C2677889
UMLS 71 C2677889

Summaries for Protoporphyria, Erythropoietic, X-Linked

UniProtKB/Swiss-Prot : 73 Erythropoietic protoporphyria, X-linked dominant: 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. XLDPT is characterized biochemically by a high proportion of zinc- protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.

MalaCards based summary : Protoporphyria, Erythropoietic, X-Linked, also known as protoporphyria, erythropoietic, x-linked dominant, is related to lymphoproliferative syndrome, x-linked, 1 and hemophagocytic lymphohistiocytosis, familial, 1. An important gene associated with Protoporphyria, Erythropoietic, X-Linked is ALAS2 (5'-Aminolevulinate Synthase 2). The drugs Aminolevulinic acid and Isoniazid have been mentioned in the context of this disorder. Affiliated tissues include liver and skin, and related phenotypes are elevated hepatic transaminase and cholelithiasis

OMIM : 56 X-linked erythropoietic protoporphyria (XLEPP) is a metabolic disorder of heme biosynthesis characterized by onset in early childhood of severe photosensitivity associated with decreased iron stores and increased erythrocyte zinc- and metal-free protoporphyrin. Some patients may develop liver disease or gallstones (summary by Ducamp et al., 2013). For a discussion of genetic heterogeneity of erythropoietic protoporphyria, see EPP1 (177000). (300752)

Related Diseases for Protoporphyria, Erythropoietic, X-Linked

Diseases related to Protoporphyria, Erythropoietic, X-Linked via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 lymphoproliferative syndrome, x-linked, 1 12.6
2 hemophagocytic lymphohistiocytosis, familial, 1 11.4
3 porphyria 11.3
4 lymphoproliferative syndrome 10.7
5 agammaglobulinemia 10.6
6 pfeiffer syndrome 10.5
7 aplastic anemia 10.4
8 pulmonary fibrosis and/or bone marrow failure, telomere-related, 2 10.4
9 protoporphyria, erythropoietic, 1 10.3
10 x-linked protoporphyria 10.3
11 lymphoma, hodgkin, classic 10.3
12 lymphoma, non-hodgkin, familial 10.3
13 b-cell lymphoma 10.3
14 immune deficiency disease 10.2
15 agammaglobulinemia, x-linked 10.2
16 hemophagocytic lymphohistiocytosis 10.2
17 lymphoma 10.2
18 vasculitis 10.2
19 acute graft versus host disease 10.2
20 anemia, x-linked, with or without neutropenia and/or platelet abnormalities 10.2
21 exanthem 10.2
22 hemosiderosis 10.2
23 iron metabolism disease 10.2
24 sideroblastic anemia 10.2
25 erythropoietic protoporphyria, autosomal recessive 10.2
26 rare hereditary hemochromatosis 10.2
27 autoimmune disease 10.1
28 burkitt lymphoma 10.1
29 kaposi sarcoma 10.1
30 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.1
31 leukemia, acute lymphoblastic 10.1
32 amnestic disorder 10.1
33 pancytopenia 10.1
34 central nervous system vasculitis 10.1
35 pathologic nystagmus 10.1
36 lymphomatoid granulomatosis 10.1

Graphical network of the top 20 diseases related to Protoporphyria, Erythropoietic, X-Linked:



Diseases related to Protoporphyria, Erythropoietic, X-Linked

Symptoms & Phenotypes for Protoporphyria, Erythropoietic, X-Linked

Human phenotypes related to Protoporphyria, Erythropoietic, X-Linked:

31
# Description HPO Frequency HPO Source Accession
1 elevated hepatic transaminase 31 occasional (7.5%) HP:0002910
2 cholelithiasis 31 occasional (7.5%) HP:0001081
3 iron deficiency anemia 31 occasional (7.5%) HP:0001891
4 cutaneous photosensitivity 31 HP:0000992
5 increased erythrocyte protoporphyrin concentration 31 HP:0012187

Symptoms via clinical synopsis from OMIM:

56
Hematology:
iron deficiency
iron-deficiency anemia (in some patients)
increased erythrocyte zinc- and metal-free protoporphyrin

Abdomen Biliary Tract:
gallstones (in some patients)

Abdomen Liver:
abnormal liver function (in some patients)

Skin Nails Hair Skin:
photosensitivity, severe

Clinical features from OMIM:

300752

Drugs & Therapeutics for Protoporphyria, Erythropoietic, X-Linked

Drugs for Protoporphyria, Erythropoietic, X-Linked (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Aminolevulinic acid Approved 106-60-5 137
2
Isoniazid Approved, Investigational 54-85-3 3767
3
Protoporphyrin IX Experimental 553-12-8
4 Anti-Infective Agents
5 Lipid Regulating Agents
6 Antitubercular Agents
7 Anti-Bacterial Agents
8 Antimetabolites
9 Hypolipidemic Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Quantification of the Effects of Isoniazid Treatment on Erythrocyte and Plasma Protoporphyrin IX Concentration and Plasma Aminolevulinic Acid in Patients With Erythropoietic Protoporphyria Terminated NCT01550705 Isoniazid

Search NIH Clinical Center for Protoporphyria, Erythropoietic, X-Linked

Genetic Tests for Protoporphyria, Erythropoietic, X-Linked

Genetic tests related to Protoporphyria, Erythropoietic, X-Linked:

# Genetic test Affiliating Genes
1 Protoporphyria, Erythropoietic, X-Linked 29 ALAS2

Anatomical Context for Protoporphyria, Erythropoietic, X-Linked

MalaCards organs/tissues related to Protoporphyria, Erythropoietic, X-Linked:

40
Liver, Skin

Publications for Protoporphyria, Erythropoietic, X-Linked

Articles related to Protoporphyria, Erythropoietic, X-Linked:

# Title Authors PMID Year
1
Molecular and functional analysis of the C-terminal region of human erythroid-specific 5-aminolevulinic synthase associated with X-linked dominant protoporphyria (XLDPP). 6 56
23263862 2013
2
C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. 56 6
18760763 2008
3
X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria. 56
25615817 2016
4
X-Linked Protoporphyria 6
23409301 2013
5
Porphyrias and photosensitivity: pathophysiology for the clinician. 61
30296862 2018

Variations for Protoporphyria, Erythropoietic, X-Linked

ClinVar genetic disease variations for Protoporphyria, Erythropoietic, X-Linked:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ALAS2 NM_000032.5(ALAS2):c.1702_1705AGTG[1] (p.Glu569fs)short repeat Pathogenic 10482 rs387906472 X:55035668-55035671 X:55009235-55009238
2 ALAS2 NM_000032.5(ALAS2):c.1699_1700del (p.Met567fs)deletion Pathogenic 10483 rs387906473 X:55035677-55035678 X:55009244-55009245
3 ALAS2 NM_000032.5(ALAS2):c.1642C>T (p.Gln548Ter)SNV Pathogenic 60673 rs397514730 X:55035735-55035735 X:55009302-55009302
4 ALAS2 NM_000032.5(ALAS2):c.1651_1676del (p.Ser551fs)deletion Pathogenic 60674 rs879255567 X:55035701-55035726 X:55009268-55009293
5 ALAS2 NM_000032.5(ALAS2):c.1757A>T (p.Tyr586Phe)SNV Uncertain significance 40978 rs139596860 X:55035620-55035620 X:55009187-55009187

Expression for Protoporphyria, Erythropoietic, X-Linked

Search GEO for disease gene expression data for Protoporphyria, Erythropoietic, X-Linked.

Pathways for Protoporphyria, Erythropoietic, X-Linked

GO Terms for Protoporphyria, Erythropoietic, X-Linked

Sources for Protoporphyria, Erythropoietic, X-Linked

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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