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Protoporphyria, erythropoietic, X-linked(XLEPP)

MedGen UID:
394385
Concept ID:
C2677889
Disease or Syndrome
Synonyms: ERYTHROHEPATIC PROTOPORPHYRIA, X-LINKED; Erythropoietic Protoporphyria, X-Linked Dominant; PROTOPORPHYRIA, ERYTHROPOIETIC, X-LINKED DOMINANT; X-Linked Protoporphyria; XLEPP
Modes of inheritance:
X-linked dominant inheritance
MedGen UID:
376232
Concept ID:
C1847879
Finding
 
Gene: ALAS2
Cytogenetic location: Xp11.21
OMIM: 300752

Disease characteristics

Excerpted from the GeneReview: X-Linked Protoporphyria
X-linked protoporphyria (XLP) is characterized in affected males by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within minutes of sun/light exposure and may be accompanied by swelling and redness. Vesicular lesions are uncommon. Pain, which may seem out of proportion to the visible skin lesions, may persist for hours or days after the initial phototoxic reaction. Photosensitivity usually remains for life. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. An unknown proportion of individuals with XLP develop liver disease. Except for those with advanced liver disease, life expectancy is not reduced. The phenotype in heterozygous females ranges from asymptomatic to as severe as affected males. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Manisha Balwani  |  Joseph Bloomer  |  Robert Desnick   view full author information

Additional descriptions

From OMIM
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 phenotypic description of erythropoietic protoporphyria, see 177000.  http://www.omim.org/entry/300752
From GHR
Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. Heme is a vital molecule for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is a component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood). Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. Some types of porphyria, called cutaneous porphyrias, primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria, hepatoerythropoietic porphyria, and porphyria cutanea tarda. Other types of porphyria, called acute porphyrias, primarily affect the nervous system. These disorders are described as "acute" because their signs and symptoms appear quickly and usually last a short time. Episodes of acute porphyria can cause abdominal pain, vomiting, constipation, and diarrhea. During an episode, a person may also experience muscle weakness, seizures, fever, and mental changes such as anxiety and hallucinations. These signs and symptoms can be life-threatening, especially if the muscles that control breathing become paralyzed. Acute porphyrias include acute intermittent porphyria and ALAD deficiency porphyria. Two other forms of porphyria, hereditary coproporphyria and variegate porphyria, can have both acute and cutaneous symptoms. The porphyrias can also be split into erythropoietic and hepatic types, depending on where damaging compounds called porphyrins and porphyrin precursors first build up in the body. In erythropoietic porphyrias, these compounds originate in the bone marrow. Erythropoietic porphyrias include erythropoietic protoporphyria and congenital erythropoietic porphyria. Health problems associated with erythropoietic porphyrias include a low number of red blood cells (anemia) and enlargement of the spleen (splenomegaly). The other types of porphyrias are considered hepatic porphyrias. In these disorders, porphyrins and porphyrin precursors originate primarily in the liver, leading to abnormal liver function and an increased risk of developing liver cancer. Environmental factors can strongly influence the occurrence and severity of signs and symptoms of porphyria. Alcohol, smoking, certain drugs, hormones, other illnesses, stress, and dieting or periods without food (fasting) can all trigger the signs and symptoms of some forms of the disorder. Additionally, exposure to sunlight worsens the skin damage in people with cutaneous porphyrias.  http://ghr.nlm.nih.gov/condition/porphyria

Clinical features

Cholelithiasis
MedGen UID:
504715
Concept ID:
CN001014
Finding
Hard, pebble-like deposits that form within the `gallbladder` (FMA:7202).
Elevated hepatic transaminases
MedGen UID:
505403
Concept ID:
CN002632
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Cutaneous photosensitivity
MedGen UID:
428240
Concept ID:
CN000929
Finding
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Increased erythrocyte protoporphyrin concentration
MedGen UID:
489657
Concept ID:
CN167913
Finding
An increased concentration of `protoporphyrins` (CHEBI:26361) in erythrocytes.

Recent clinical studies

Etiology

García-Martínez FJ, Gutiérrez-González E, Alonso-González J, Vega A, Santamariña M, Rodríguez-Granados MT, Toribio J
Dermatology 2013;227(3):238-42. Epub 2013 Oct 15 doi: 10.1159/000354387. [Epub ahead of print] PMID: 24135682
Balwani M, Doheny D, Bishop DF, Nazarenko I, Yasuda M, Dailey HA, Anderson KE, Bissell DM, Bloomer J, Bonkovsky HL, Phillips JD, Liu L, Desnick RJ; Porphyrias Consortium of the National Institutes of Health Rare Diseases Clinical Research Network
Mol Med 2013 Apr 30;19:26-35. doi: 10.2119/molmed.2012.00340. [Epub ahead of print] PMID: 23364466Free PMC Article
Minder EI
Expert Opin Investig Drugs 2010 Dec;19(12):1591-602. Epub 2010 Nov 13 doi: 10.1517/13543784.2010.535515. [Epub ahead of print] PMID: 21073357
Lecha M, Puy H, Deybach JC
Orphanet J Rare Dis 2009 Sep 10;4:19. doi: 10.1186/1750-1172-4-19. [Epub ahead of print] PMID: 19744342Free PMC Article
Elder GH, Gouya L, Whatley SD, Puy H, Badminton MN, Deybach JC
Cell Mol Biol (Noisy-le-grand) 2009 Jul 1;55(2):118-26. PMID: 19656460

Diagnosis

García-Martínez FJ, Gutiérrez-González E, Alonso-González J, Vega A, Santamariña M, Rodríguez-Granados MT, Toribio J
Dermatology 2013;227(3):238-42. Epub 2013 Oct 15 doi: 10.1159/000354387. [Epub ahead of print] PMID: 24135682
Balwani M, Doheny D, Bishop DF, Nazarenko I, Yasuda M, Dailey HA, Anderson KE, Bissell DM, Bloomer J, Bonkovsky HL, Phillips JD, Liu L, Desnick RJ; Porphyrias Consortium of the National Institutes of Health Rare Diseases Clinical Research Network
Mol Med 2013 Apr 30;19:26-35. doi: 10.2119/molmed.2012.00340. [Epub ahead of print] PMID: 23364466Free PMC Article
Balwani M, Desnick RJ
Hematology Am Soc Hematol Educ Program 2012;2012:19-27. doi: 10.1182/asheducation-2012.1.19. PMID: 23233556
Whatley SD, Mason NG, Holme SA, Anstey AV, Elder GH, Badminton MN
Br J Dermatol 2010 Mar;162(3):642-6. Epub 2010 Jan 22 doi: 10.1111/j.1365-2133.2010.09631.x. [Epub ahead of print] PMID: 20105171
Lecha M, Puy H, Deybach JC
Orphanet J Rare Dis 2009 Sep 10;4:19. doi: 10.1186/1750-1172-4-19. [Epub ahead of print] PMID: 19744342Free PMC Article

Therapy

García-Martínez FJ, Gutiérrez-González E, Alonso-González J, Vega A, Santamariña M, Rodríguez-Granados MT, Toribio J
Dermatology 2013;227(3):238-42. Epub 2013 Oct 15 doi: 10.1159/000354387. [Epub ahead of print] PMID: 24135682
Minder EI
Expert Opin Investig Drugs 2010 Dec;19(12):1591-602. Epub 2010 Nov 13 doi: 10.1517/13543784.2010.535515. [Epub ahead of print] PMID: 21073357

Prognosis

Whatley SD, Badminton MN
Ann Clin Biochem 2013 May;50(Pt 3):204-16. doi: 10.1177/0004563212473278. PMID: 23605133
To-Figueras J, Ducamp S, Clayton J, Badenas C, Delaby C, Ged C, Lyoumi S, Gouya L, de Verneuil H, Beaumont C, Ferreira GC, Deybach JC, Herrero C, Puy H
Blood 2011 Aug 11;118(6):1443-51. Epub 2011 Jun 7 doi: 10.1182/blood-2011-03-342873. [Epub ahead of print] PMID: 21653323
Whatley SD, Mason NG, Holme SA, Anstey AV, Elder GH, Badminton MN
Br J Dermatol 2010 Mar;162(3):642-6. Epub 2010 Jan 22 doi: 10.1111/j.1365-2133.2010.09631.x. [Epub ahead of print] PMID: 20105171
Lecha M, Puy H, Deybach JC
Orphanet J Rare Dis 2009 Sep 10;4:19. doi: 10.1186/1750-1172-4-19. [Epub ahead of print] PMID: 19744342Free PMC Article

Clinical prediction guides

Takeichi T, Nanda A, Liu L, Salam A, Campbell P, Fong K, Akiyama M, Ozoemena L, Stone KL, Al-Ajmi H, Simpson MA, McGrath JA
Exp Dermatol 2013 Dec;22(12):825-31. doi: 10.1111/exd.12276. PMID: 24279917
García-Martínez FJ, Gutiérrez-González E, Alonso-González J, Vega A, Santamariña M, Rodríguez-Granados MT, Toribio J
Dermatology 2013;227(3):238-42. Epub 2013 Oct 15 doi: 10.1159/000354387. [Epub ahead of print] PMID: 24135682
Whatley SD, Badminton MN
Ann Clin Biochem 2013 May;50(Pt 3):204-16. doi: 10.1177/0004563212473278. PMID: 23605133
To-Figueras J, Ducamp S, Clayton J, Badenas C, Delaby C, Ged C, Lyoumi S, Gouya L, de Verneuil H, Beaumont C, Ferreira GC, Deybach JC, Herrero C, Puy H
Blood 2011 Aug 11;118(6):1443-51. Epub 2011 Jun 7 doi: 10.1182/blood-2011-03-342873. [Epub ahead of print] PMID: 21653323
Whatley SD, Mason NG, Holme SA, Anstey AV, Elder GH, Badminton MN
Br J Dermatol 2010 Mar;162(3):642-6. Epub 2010 Jan 22 doi: 10.1111/j.1365-2133.2010.09631.x. [Epub ahead of print] PMID: 20105171

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