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Variegate porphyria(VP)

MedGen UID:
58118
Concept ID:
C0162532
Disease or Syndrome
Synonyms: Porphyria, South African type; PPOX deficiency; Protoporphyrinogen oxidase deficiency; VP
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Protoporphyrinogen oxidase deficiency (58275005); VP - Variegate porphyria (58275005); Porphyria variegata (58275005); Variegate porphyria (58275005); Protocoproporphyria (58275005); Dean-Barnes syndrome (58275005); Mixed porphyria (58275005)
 
Genes (locations): HFE (6p22.2); PPOX (1q23.3)
OMIM®: 176200
Orphanet: ORPHA79473

Disease characteristics

Excerpted from the GeneReview: Variegate Porphyria
Variegate porphyria (VP) is a cutaneous porphyria (with chronic blistering skin lesions) and an acute porphyria (with severe episodic neurovisceral symptoms). The most common manifestation of VP is adult-onset cutaneous blistering lesions (subepidermal vesicles, bullae, and erosions that crust over and heal slowly) of sun-exposed skin, especially the hands and face. Other chronic skin findings include milia, scarring, thickening, and areas of decreased and increased skin pigmentation. Facial hyperpigmentation and hypertrichosis may occur. Cutaneous manifestations may improve in winter, and be less prevalent in northern regions and in dark-skinned individuals. Acute neurovisceral symptoms can occur any time after puberty, but less often in the elderly. Acute manifestations are highly variable, but may be similar from episode to episode in a patient with recurrent attacks; not all symptoms are present in a single episode; and acute symptoms may become chronic. Symptoms are more common in women than men. The most common symptoms are abdominal pain; constipation; pain in the back, chest, and extremities; anxiety; seizures; and a primarily motor neuropathy resulting in muscle weakness that may progress to quadriparesis and respiratory paralysis. Psychiatric disturbances and autonomic neuropathy can also be observed. Acute attacks may be severe and are potentially fatal. [from GeneReviews]
Authors:
Ashwani K Singal  |  Karl E Anderson   view full author information

Additional descriptions

From OMIM
Variegate porphyria is characterized by cutaneous manifestations, including increased photosensitivity, blistering, skin fragility with chronic scarring of sun-exposed areas, and postinflammatory hyperpigmentation. Acute exacerbations of VP include abdominal pain, the passage of dark urine, and neuropsychiatric symptoms that characterize the acute hepatic porphyrias, such as bulbar paralysis, quadriplegia, motor neuropathy, and weakness of the limbs. In heterozygotes, PPOX activity is decreased by about 50% (summary by Frank et al., 1998).  http://www.omim.org/entry/176200
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.  https://ghr.nlm.nih.gov/condition/porphyria

Clinical features

Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
A disorder affecting the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.
Psychosis
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes of personality and thought patterns often accompanied by hallucinations and delusional beliefs.
Tachycardia
MedGen UID:
21453
Concept ID:
C0039231
Finding
A rapid heartrate that exceeds the range of the normal resting heartrate for age.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Porphyrinuria
MedGen UID:
57493
Concept ID:
C0151861
Disease or Syndrome
Abnormally increased excretion of porphyrins in the urine.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVVariegate porphyria
Follow this link to review classifications for Variegate porphyria in Orphanet.

Recent clinical studies

Etiology

Ferrer MD, Tauler P, Sureda A, Palacín C, Tur JA, Pons A
Eur J Clin Invest 2013 Jul;43(7):668-78. Epub 2013 Apr 20 doi: 10.1111/eci.12091. PMID: 23601071
Schneider-Yin X, van Tuyll van Serooskerken AM, Went P, Tyblewski W, Poblete-Gutiérrez P, Minder EI, Frank J
Acta Derm Venereol 2010 Sep;90(5):512-5. doi: 10.2340/00015555-0870. PMID: 20814629
Reiser M, Eickmann S, Haverkamp T, Finckh U
Obes Rev 2010 Apr;11(4):329-31. Epub 2009 Oct 21 doi: 10.1111/j.1467-789X.2009.00670.x. PMID: 19845869
Ferrer MD, Tauler P, Sureda A, Romaguera D, Llompart I, Palacin C, Orfila J, Tur JA, Pons A
Redox Rep 2009;14(2):69-74. doi: 10.1179/135100009X392502. PMID: 19389274
Hift RJ, Meissner PN
Medicine (Baltimore) 2005 Jan;84(1):48-60. PMID: 15643299

Diagnosis

Kuźmiński A, Aporowicz M, Brol M, Żołnowska A, Masternak M
J Clin Anesth 2016 Dec;35:114-117. Epub 2016 Aug 11 doi: 10.1016/j.jclinane.2016.06.014. PMID: 27871506
Granata BX, Parera VE, Batlle A, Rossetti MV
Hum Hered 2015;80(3):139-43. Epub 2016 May 24 doi: 10.1159/000445749. PMID: 27216491
Luvai A, Mbagaya W, Narayanan D, Degg T, Toogood G, Wyatt JI, Swinson D, Hall CJ, Barth JH
Ann Clin Biochem 2015 May;52(Pt 3):407-12. Epub 2014 Oct 9 doi: 10.1177/0004563214557568. PMID: 25301776
Pinder VA, Holden ST, Deshpande C, Siddiqui A, Mellerio JE, Wraige E, Powell AM
Clin Exp Dermatol 2013 Oct;38(7):737-40. doi: 10.1111/ced.12071. PMID: 24073655
Hift RJ, Peters TJ, Meissner PN
J Clin Pathol 2012 Mar;65(3):200-5. Epub 2011 Nov 2 doi: 10.1136/jclinpath-2011-200276. PMID: 22049218

Therapy

Kuźmiński A, Aporowicz M, Brol M, Żołnowska A, Masternak M
J Clin Anesth 2016 Dec;35:114-117. Epub 2016 Aug 11 doi: 10.1016/j.jclinane.2016.06.014. PMID: 27871506
Ferrer MD, Tauler P, Sureda A, Palacín C, Tur JA, Pons A
Eur J Clin Invest 2013 Jul;43(7):668-78. Epub 2013 Apr 20 doi: 10.1111/eci.12091. PMID: 23601071
Ferrer MD, Tauler P, Sureda A, Palacín C, Tur JA, Pons A
Br J Nutr 2010 Jan;103(1):69-76. Epub 2009 Nov 3 doi: 10.1017/S0007114509991413. PMID: 19883519
Reiser M, Eickmann S, Haverkamp T, Finckh U
Obes Rev 2010 Apr;11(4):329-31. Epub 2009 Oct 21 doi: 10.1111/j.1467-789X.2009.00670.x. PMID: 19845869
Hift RJ, Meissner PN
Medicine (Baltimore) 2005 Jan;84(1):48-60. PMID: 15643299

Prognosis

Tsuchiya Y, Hoshino J, Suwabe T, Sumida K, Hiramatsu R, Mise K, Hasegawa E, Yamanouchi M, Hayami N, Sawa N, Arizono K, Hara S, Takaichi K, Fujii T, Ubara Y
Amyloid 2013 Dec;20(4):272-4. Epub 2013 Oct 16 doi: 10.3109/13506129.2013.837390. PMID: 24131077Free PMC Article
Wang B, Wen X, Qin X, Wang Z, Tan Y, Shen Y, Xi Z
J Biol Chem 2013 Apr 26;288(17):11731-40. Epub 2013 Mar 6 doi: 10.1074/jbc.M113.459768. PMID: 23467411Free PMC Article
Hift RJ, Peters TJ, Meissner PN
J Clin Pathol 2012 Mar;65(3):200-5. Epub 2011 Nov 2 doi: 10.1136/jclinpath-2011-200276. PMID: 22049218
Schneider-Yin X, van Tuyll van Serooskerken AM, Went P, Tyblewski W, Poblete-Gutiérrez P, Minder EI, Frank J
Acta Derm Venereol 2010 Sep;90(5):512-5. doi: 10.2340/00015555-0870. PMID: 20814629
Hift RJ, Meissner PN
Medicine (Baltimore) 2005 Jan;84(1):48-60. PMID: 15643299

Clinical prediction guides

Fiorentino V, Brancaleoni V, Granata F, Graziadei G, Di Pierro E
Blood Cells Mol Dis 2016 Oct;61:48-53. Epub 2016 Aug 17 doi: 10.1016/j.bcmd.2016.08.002. PMID: 27667166
Ferrer MD, Tauler P, Sureda A, Palacín C, Tur JA, Pons A
Eur J Clin Invest 2013 Jul;43(7):668-78. Epub 2013 Apr 20 doi: 10.1111/eci.12091. PMID: 23601071
Wang B, Wen X, Qin X, Wang Z, Tan Y, Shen Y, Xi Z
J Biol Chem 2013 Apr 26;288(17):11731-40. Epub 2013 Mar 6 doi: 10.1074/jbc.M113.459768. PMID: 23467411Free PMC Article
Hift RJ, Peters TJ, Meissner PN
J Clin Pathol 2012 Mar;65(3):200-5. Epub 2011 Nov 2 doi: 10.1136/jclinpath-2011-200276. PMID: 22049218
Ferrer MD, Sureda A, Tauler P, Palacín C, Tur JA, Pons A
Br J Haematol 2010 Jun;149(5):759-67. Epub 2010 Mar 12 doi: 10.1111/j.1365-2141.2010.08149.x. PMID: 20331452

Recent systematic reviews

Baravelli CM, Sandberg S, Aarsand AK, Nilsen RM, Tollånes MC
J Intern Med 2017 Sep;282(3):229-240. Epub 2017 Jul 20 doi: 10.1111/joim.12646. PMID: 28730628
Stein P, Badminton M, Barth J, Rees D, Stewart MF; British and Irish Porphyria Network.
Ann Clin Biochem 2013 May;50(Pt 3):217-23. doi: 10.1177/0004563212474555. PMID: 23605132
du Plessis N, Kimberg M, Zaahl MG, Sadie A, Venter M, van der Merwe L, Louw A, Warnich L
Cell Mol Biol (Noisy-le-grand) 2009 Jul 1;55(2):20-30. PMID: 19656447

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