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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
SNOMED CT: Protoporphyrinogen oxidase deficiency (58275005); VP - Variegate porphyria (58275005); Porphyria variegata (58275005); Variegate porphyria (58275005); South African porphyria (58275005); South African genetic porphyria (58275005); Protocoproporphyria (58275005); Dean-Barnes syndrome (58275005); Mixed porphyria (58275005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: 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.
 
Gene (location): PPOX (1q23.3)
 
Monarch Initiative: MONDO:0008297
OMIM®: 176200
Orphanet: ORPHA79473

Disease characteristics

Excerpted from the GeneReview: Variegate Porphyria
Variegate porphyria (VP) is both 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 person with recurrent attacks; not all manifestations are present in a single episode; and acute symptoms may become chronic. Symptoms are more common in women than men. The most common manifestations 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 (VP) 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. VP is inherited as an autosomal dominant trait with incomplete penetrance. Clinical manifestations do not usually present before puberty, and PPOX activity is decreased by about 50% (summary by Frank et al., 1998).  http://www.omim.org/entry/176200
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.

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.

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.

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
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.
Porphyrinuria
MedGen UID:
57493
Concept ID:
C0151861
Disease or Syndrome
Abnormally increased excretion of porphyrins in the urine.
Elevated urinary delta-aminolevulinic acid
MedGen UID:
341286
Concept ID:
C1848702
Finding
An increased concentration of 5-aminolevulinic acid (CHEBI:17549) in the urine.
Increased urinary porphobilinogen
MedGen UID:
868601
Concept ID:
C4023000
Finding
The concentration of porphobilinogen in the urine, normalized for urine concentration, is above the upper limit of normal.
Tachycardia
MedGen UID:
21453
Concept ID:
C0039231
Finding
A rapid heartrate that exceeds the range of the normal resting heartrate for age.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
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.
Increased fecal protoporphyrin concentration
MedGen UID:
1814410
Concept ID:
C5676846
Finding
Abnormally high concentration of protoporphyrin (derivative of porphyrin with propionic acid groups) in feces.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
Paralysis
MedGen UID:
105510
Concept ID:
C0522224
Finding
Paralysis of voluntary muscles means loss of contraction due to interruption of one or more motor pathways from the brain to the muscle fibers. Although the word paralysis is often used interchangeably to mean either complete or partial loss of muscle strength, it is preferable to use paralysis or plegia for complete or severe loss of muscle strength, and paresis for partial or slight loss. Motor paralysis results from deficits of the upper motor neurons (corticospinal, corticobulbar, or subcorticospinal). Motor paralysis is often accompanied by an impairment in the facility of movement.
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.

Professional guidelines

PubMed

Wang B, Bonkovsky HL, Lim JK, Balwani M
Gastroenterology 2023 Mar;164(3):484-491. Epub 2023 Jan 13 doi: 10.1053/j.gastro.2022.11.034. PMID: 36642627Free PMC Article
Ricci A, Ventura P
Expert Rev Clin Pharmacol 2022 Apr;15(4):383-393. Epub 2022 May 11 doi: 10.1080/17512433.2022.2075848. PMID: 35531651
Gilles A, Vermeersch S, Vermeersch P, Wolff F, Cotton F, Tilleux S, Cassiman D
Acta Clin Belg 2022 Aug;77(4):735-741. Epub 2021 Aug 7 doi: 10.1080/17843286.2021.1961056. PMID: 34369323

Curated

Orphanet emergency guideline: Cutaneous porphyrias, 2007

Orphanet, Acute hepatic porphyria neuro-visceral crisis, 2007

Recent clinical studies

Etiology

Wang B, Bonkovsky HL, Lim JK, Balwani M
Gastroenterology 2023 Mar;164(3):484-491. Epub 2023 Jan 13 doi: 10.1053/j.gastro.2022.11.034. PMID: 36642627Free PMC Article
Wylie K, Testai FD
Curr Neurol Neurosci Rep 2022 Jul;22(7):355-362. Epub 2022 Jun 4 doi: 10.1007/s11910-022-01205-7. PMID: 35665475
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
Besur S, Schmeltzer P, Bonkovsky HL
J Emerg Med 2015 Sep;49(3):305-12. Epub 2015 Jul 7 doi: 10.1016/j.jemermed.2015.04.034. PMID: 26159905
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

Diagnosis

Wang B, Bonkovsky HL, Lim JK, Balwani M
Gastroenterology 2023 Mar;164(3):484-491. Epub 2023 Jan 13 doi: 10.1053/j.gastro.2022.11.034. PMID: 36642627Free PMC Article
Muschalek W, Hermasch MA, Poblete-Gutiérrez P, Frank J
J Dtsch Dermatol Ges 2022 Mar;20(3):316-331. doi: 10.1111/ddg.14743. PMID: 35304965
Gerischer LM, Scheibe F, Nümann A, Köhnlein M, Stölzel U, Meisel A
Brain Behav 2021 Nov;11(11):e2389. Epub 2021 Oct 17 doi: 10.1002/brb3.2389. PMID: 34661997Free PMC Article
Stölzel U, Doss MO, Schuppan D
Gastroenterology 2019 Aug;157(2):365-381.e4. Epub 2019 May 11 doi: 10.1053/j.gastro.2019.04.050. PMID: 31085196
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

Therapy

Wang B, Bonkovsky HL, Lim JK, Balwani M
Gastroenterology 2023 Mar;164(3):484-491. Epub 2023 Jan 13 doi: 10.1053/j.gastro.2022.11.034. PMID: 36642627Free PMC Article
Besur S, Schmeltzer P, Bonkovsky HL
J Emerg Med 2015 Sep;49(3):305-12. Epub 2015 Jul 7 doi: 10.1016/j.jemermed.2015.04.034. PMID: 26159905
Schulenburg-Brand D, Katugampola R, Anstey AV, Badminton MN
Dermatol Clin 2014 Jul;32(3):369-84, ix. Epub 2014 May 5 doi: 10.1016/j.det.2014.03.001. PMID: 24891059
Baran R, Juhlin L
Photodermatol Photoimmunol Photomed 2002 Aug;18(4):202-7. doi: 10.1034/j.1600-0781.2002.00760.x. PMID: 12390677
Moore MR, McColl KE, Goldberg A
Diabete Metab 1979 Dec;5(4):323-36. PMID: 398301

Prognosis

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
Arora S, Young S, Kodali S, Singal AK
Indian J Gastroenterol 2016 Nov;35(6):405-418. Epub 2016 Oct 31 doi: 10.1007/s12664-016-0698-0. PMID: 27796941
Besur S, Schmeltzer P, Bonkovsky HL
J Emerg Med 2015 Sep;49(3):305-12. Epub 2015 Jul 7 doi: 10.1016/j.jemermed.2015.04.034. PMID: 26159905
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
Kauppinen R
Photodermatol Photoimmunol Photomed 1998 Apr;14(2):48-51. doi: 10.1111/j.1600-0781.1998.tb00010.x. PMID: 9638723

Clinical prediction guides

Farrell CP, Nicolas G, Desnick RJ, Parker CJ, Lamoril J, Gouya L, Karim Z, Tchernitchko D, Chan B, Puy H, Phillips JD
Blood Adv 2022 Feb 8;6(3):760-766. doi: 10.1182/bloodadvances.2021005484. PMID: 34724702Free 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
Baran R, Juhlin L
Photodermatol Photoimmunol Photomed 2002 Aug;18(4):202-7. doi: 10.1034/j.1600-0781.2002.00760.x. PMID: 12390677
Doss MO, Kühnel A, Gross U
Alcohol Alcohol 2000 Mar-Apr;35(2):109-25. doi: 10.1093/alcalc/35.2.109. PMID: 10787385
Cripps DJ
IARC Sci Publ 1986;(77):549-66. PMID: 3298037

Recent systematic reviews

Burfield L, Rutter KJ, Thompson B, Marjanovic EJ, Neale RE, Rhodes LE
J Eur Acad Dermatol Venereol 2023 Mar;37(3):511-520. Epub 2022 Dec 3 doi: 10.1111/jdv.18772. PMID: 36433668
Jaramillo-Calle DA, Solano JM, Rabinstein AA, Bonkovsky HL
Mol Genet Metab 2019 Nov;128(3):242-253. Epub 2019 Nov 1 doi: 10.1016/j.ymgme.2019.10.011. PMID: 31706631

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • Orphanet, 2007
      Orphanet emergency guideline: Cutaneous porphyrias, 2007
    • Orphanet, 2007
      Orphanet, Acute hepatic porphyria neuro-visceral crisis, 2007

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