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Protoporphyria, erythropoietic, 1(EPP1)

MedGen UID:
1643471
Concept ID:
C4692546
Disease or Syndrome
Synonyms: EPP1; Erythropoietic Protoporphyria, Autosomal Recessive; Ferrochelatase deficiency; Heme synthetase deficiency
 
Gene (location): FECH (18q21.31)
 
Monarch Initiative: MONDO:0008319
OMIM®: 177000

Disease characteristics

Erythropoietic protoporphyria (EPP) is characterized by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within 30 minutes after exposure to sun or ultraviolet light and may be accompanied by swelling and redness. Symptoms (which may seem out of proportion to the visible skin lesions) may persist for hours or days after the initial phototoxic reaction. Photosensitivity 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. Approximately 20%-30% of individuals with EPP have some degree of liver dysfunction, which is typically mild with slight elevations of the liver enzymes. Up to 5% may develop more advanced liver disease which may be accompanied by motor neuropathy similar to that seen in the acute porphyrias. [from GeneReviews]
Authors:
Manisha Balwani  |  Joseph Bloomer  |  Robert Desnick, et. al.   view full author information

Additional description

From MedlinePlus Genetics
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.

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.

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.

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.

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).  https://medlineplus.gov/genetics/condition/porphyria

Clinical features

From HPO
Cholelithiasis
MedGen UID:
3039
Concept ID:
C0008350
Disease or Syndrome
Hard, pebble-like deposits that form within the gallbladder.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Eczema
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Pruritus
MedGen UID:
19534
Concept ID:
C0033774
Sign or Symptom
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.

Professional guidelines

PubMed

Fung MA, Murphy MJ, Hoss DM, Berke A, Grant-Kels JM
Am J Dermatopathol 2003 Aug;25(4):287-90. doi: 10.1097/00000372-200308000-00002. PMID: 12876485

Recent clinical studies

Etiology

Balwani M, Bonkovsky HL, Levy C, Anderson KE, Bissell DM, Parker C, Takahashi F, Desnick RJ, Belongie K; Endeavor Investigators
N Engl J Med 2023 Apr 13;388(15):1376-1385. doi: 10.1056/NEJMoa2208754. PMID: 37043653
Phillips JD
Mol Genet Metab 2019 Nov;128(3):164-177. Epub 2019 Apr 22 doi: 10.1016/j.ymgme.2019.04.008. PMID: 31326287Free PMC Article
Ramanujam VS, Anderson KE
Curr Protoc Hum Genet 2015 Jul 1;86:17.20.1-17.20.26. doi: 10.1002/0471142905.hg1720s86. PMID: 26132003Free PMC Article
Lecha M, Puy H, Deybach JC
Orphanet J Rare Dis 2009 Sep 10;4:19. doi: 10.1186/1750-1172-4-19. PMID: 19744342Free PMC Article
Moore MR, McColl KE, Goldberg A
Diabete Metab 1979 Dec;5(4):323-36. PMID: 398301

Diagnosis

Raef HS, Rebeiz L, Leaf RK, Hughes O, Jiang P, ElSeht A, Anderson KE, Wheeden K, Kochevar I, Elmariah SB, Dickey AK
JAMA Dermatol 2023 Feb 1;159(2):204-208. doi: 10.1001/jamadermatol.2022.5850. PMID: 36630131Free PMC Article
Ramanujam VS, Anderson KE
Curr Protoc Hum Genet 2015 Jul 1;86:17.20.1-17.20.26. doi: 10.1002/0471142905.hg1720s86. PMID: 26132003Free PMC Article
Mykletun M, Aarsand AK, Støle E, Villanger JH, Tollånes MC, Baravelli C, Sandberg S
Tidsskr Nor Laegeforen 2014 Apr 29;134(8):831-6. doi: 10.4045/tidsskr.13.0649. PMID: 24780981
Lecha M, Puy H, Deybach JC
Orphanet J Rare Dis 2009 Sep 10;4:19. doi: 10.1186/1750-1172-4-19. PMID: 19744342Free PMC Article
Elder GH
Semin Dermatol 1990 Mar;9(1):63-9. PMID: 2203445

Therapy

Balwani M, Bonkovsky HL, Levy C, Anderson KE, Bissell DM, Parker C, Takahashi F, Desnick RJ, Belongie K; Endeavor Investigators
N Engl J Med 2023 Apr 13;388(15):1376-1385. doi: 10.1056/NEJMoa2208754. PMID: 37043653
Heerfordt IM, Lerche CM, Wulf HC
Photodiagnosis Photodyn Ther 2022 Jun;38:102793. Epub 2022 Mar 2 doi: 10.1016/j.pdpdt.2022.102793. PMID: 35245673
Wensink D, Wagenmakers MAEM, Langendonk JG
Expert Rev Clin Pharmacol 2021 Feb;14(2):151-160. doi: 10.1080/17512433.2021.1879638. PMID: 33507118
Elder GH
Semin Dermatol 1990 Mar;9(1):63-9. PMID: 2203445
Moore MR, McColl KE, Goldberg A
Diabete Metab 1979 Dec;5(4):323-36. PMID: 398301

Prognosis

Ogasawara H, Tokodai K, Nakanishi W, Fujio A, Kashiwadate T, Shono Y, Ohta M, Ishikawa Y, Miyagi S, Fujishima F, Unno M, Kamei T
Tohoku J Exp Med 2023 Oct 7;261(2):117-122. Epub 2023 Jul 27 doi: 10.1620/tjem.2023.J061. PMID: 37495523
Yasuda M, Chen B, Desnick RJ
Mol Genet Metab 2019 Nov;128(3):320-331. Epub 2018 Nov 30 doi: 10.1016/j.ymgme.2018.11.012. PMID: 30594473Free PMC Article
Lecha M, Puy H, Deybach JC
Orphanet J Rare Dis 2009 Sep 10;4:19. doi: 10.1186/1750-1172-4-19. PMID: 19744342Free PMC Article
Holme SA, Anstey AV, Finlay AY, Elder GH, Badminton MN
Br J Dermatol 2006 Sep;155(3):574-81. doi: 10.1111/j.1365-2133.2006.07472.x. PMID: 16911284
Kondo M, Yano Y, Shirataka M, Urata G, Sassa S
Int J Hematol 2004 Jun;79(5):448-56. doi: 10.1532/ijh97.03127. PMID: 15239394

Clinical prediction guides

Dean AE, Jungwirth E, Panzitt K, Wagner M, Anakk S
Hepatol Commun 2023 Oct 1;7(10) Epub 2023 Sep 11 doi: 10.1097/HC9.0000000000000213. PMID: 37695073Free PMC Article
Ogasawara A, Ogawa K, Ide R, Ikenaga Y, Fukunaga C, Nakayama S, Tsuda M
Eur J Clin Pharmacol 2023 Jun;79(6):801-813. Epub 2023 Apr 15 doi: 10.1007/s00228-023-03476-6. PMID: 37060458Free PMC Article
Phillips JD
Mol Genet Metab 2019 Nov;128(3):164-177. Epub 2019 Apr 22 doi: 10.1016/j.ymgme.2019.04.008. PMID: 31326287Free PMC Article
Biewenga M, Matawlie RHS, Friesema ECH, Koole-Lesuis H, Langeveld M, Wilson JHP, Langendonk JG
Br J Dermatol 2017 Dec;177(6):1693-1698. Epub 2017 Nov 22 doi: 10.1111/bjd.15893. PMID: 28815553
Ghosh MC, Zhang DL, Rouault TA
Neurobiol Dis 2015 Sep;81:66-75. Epub 2015 Mar 11 doi: 10.1016/j.nbd.2015.02.026. PMID: 25771171Free PMC Article

Recent systematic reviews

Snast I, Kaftory R, Sherman S, Edel Y, Hodak E, Levi A, Lapidoth M
Photodermatol Photoimmunol Photomed 2020 Jan;36(1):29-33. Epub 2019 Aug 21 doi: 10.1111/phpp.12501. PMID: 31374130
Minder EI, Schneider-Yin X, Steurer J, Bachmann LM
Cell Mol Biol (Noisy-le-grand) 2009 Feb 16;55(1):84-97. PMID: 19268006

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