Variegate porphyria: Difference between revisions

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{{Short description|A type of porphyria affecting the skin and nervous system}}
{{Use dmy dates|date=October 2023}}
{{Infobox medical condition (new)
{{Infobox medical condition (new)
| name            = Variegate porphyria
| name            = Variegate porphyria
| synonyms     =Mixed hepatic porphyria,<ref name="Andrews" /> Mixed porphyria,<ref name="Andrews" /> South African genetic porphyria,<ref name="Andrews">{{cite book |vauthors=James, William D, Berger, Timothy G |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |location= |year=2006 |pages= |isbn=978-0-7216-2921-6 |oclc= |doi= |accessdate=|display-authors=etal}}</ref>{{rp|525}} and South African porphyria.<ref name="Bolognia">{{cite book |author1=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3= Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages= |isbn=978-1-4160-2999-1 |oclc= |doi= |accessdate=}}</ref>
| synonyms       = Mixed hepatic porphyria
| image          = Protoporphyrinogen IX.svg
| image          = Protoporphyrinogen IX.svg
| caption        = [[Protoporphyrinogen IX]]
| caption        = [[Protoporphyrinogen IX]]
| pronounce      =  
| pronounce      =  
| field          =  
| field          = [[Dermatology]], [[Medical genetics]], [[Hepatology]]
| symptoms        = skin problems,
| symptoms        = Skin photosensitivity, blistering on sun-exposed areas, abdominal pain, [[neuropathy]], [[seizures]], [[muscle weakness]]
[[Enzyme]] difficiency.
| complications  = [[Liver damage]], [[kidney disease]], [[neurological deficits]], [[skin infections]]
| complications  =  
| onset          = Typically adolescence or adulthood
| onset          =  
| duration        = Chronic, lifelong condition
| duration        =  
| types          = Hepatic porphyria
| types          =  
| causes          = Mutations in the ''[[PPOX]]'' gene affecting protoporphyrinogen oxidase
| causes          = genetic mutations.
| risks          = Family history, certain medications, fasting, hormonal changes, alcohol, smoking, stress
| risks          =  
| diagnosis      = [[Urine test]], [[plasma fluorescence scan]], genetic testing, [[porphyrin]] studies
| diagnosis      =  
| differential    = [[Acute intermittent porphyria]], [[porphyria cutanea tarda]], [[erythropoietic protoporphyria]]
| differential    =  
| prevention      = Avoidance of triggers such as alcohol, sunlight, certain drugs, and fasting
| prevention      =  
| treatment      = Symptomatic treatment, liver transplant in severe cases, avoid triggering factors
| treatment      = liver transplants.
| medication      = [[Hemin]] (for acute attacks), pain relievers, anti-nausea medications
| medication      =  
| prognosis      = Variable; generally manageable with lifestyle modifications, but attacks can be severe
| prognosis      =  
| frequency      = Rare; more prevalent in South African populations due to founder effect
| frequency      =  
| deaths          = Rare, mostly due to complications during acute attacks if untreated
| deaths          =  
}}
}}
'''Variegate porphyria''', also known by [[#Names|several other names]], is an [[autosomal dominant]] [[porphyria]]<ref>{{DorlandsDict|nine/210001837|porphyria variegata}}</ref> that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect the [[skin]]. The disorder results from low levels of the [[enzyme]] responsible for the seventh step in [[heme]] production. Heme is a vital molecule for all of the body's [[organ (anatomy)|organs]]. It is a component of [[hemoglobin]], the molecule that carries [[oxygen]] in the [[blood]].
[[Image:Autosomal dominant - en.svg|thumb|Variegate porphyria has an autosomal dominant pattern of inheritance.|left]]


==Signs and symptoms==
'''Variegate porphyria''' (VP) is a type of [[porphyria]], a group of rare metabolic disorders resulting from a deficiency of enzymes in the [[heme]] biosynthesis pathway. This condition is characterized by a combination of [[cutaneous]] and [[neurological]] symptoms due to the accumulation of porphyrins and their precursors.
When symptoms occur, they can include acute attacks (similar to [[acute intermittent porphyria]]) or skin damage. Acute attacks usually begin in adulthood and cause abdominal pain, [[vomiting]], [[diarrhoea]] and [[constipation]]. During an attack, a person may also experience muscle weakness, [[seizure]]s, and mental changes such as anxiety and [[hallucination]]s. These signs and symptoms are triggered by nongenetic factors such as certain drugs, dieting or fasting, certain [[hormone]]s and stress.


Some people with variegate porphyria have skin that is overly sensitive to [[sunlight]] ([[photosensitivity|photosensitive]]). Areas of skin exposed to the sun develop severe blistering, scarring, changes in [[pigmentation]], and increased hair growth. Exposed skin becomes fragile and is easily damaged.
==Pathophysiology==
 
Variegate porphyria is caused by a deficiency of the enzyme [[protoporphyrinogen oxidase]] (PPOX), which is the seventh enzyme in the heme biosynthetic pathway. This deficiency leads to the accumulation of porphyrins and their precursors, particularly in the liver, resulting in the clinical manifestations of the disease.
Rarely, the signs and symptoms of variegate porphyria can begin in infancy or early childhood. In such cases, the signs and symptoms are usually more severe than those starting later in life. In addition to the health problems described above, children with this disorder may have mental retardation and grow more slowly than other children.


==Genetics==
==Genetics==
Variegate porphyria is inherited in an [[autosomal dominant]] pattern, meaning that a single copy of the mutated gene in each cell is sufficient to cause the disorder. The gene responsible for VP is located on [[chromosome 1]] and is known as the PPOX gene. Mutations in this gene reduce the activity of the protoporphyrinogen oxidase enzyme.


[[Image:Autosomal dominant - en.svg|thumb|right|Variegate porphyria has an autosomal dominant pattern of inheritance.]]
==Clinical Features==
The clinical presentation of variegate porphyria can vary widely among affected individuals. The main features include:


[[Mutation]]s in the [[PPOX]] [[gene]] cause variegate porphyria.<ref name="pmid10343202">{{cite journal |vauthors=Frank J, Christiano AM |title=Variegate porphyria: past, present and future |journal=Skin Pharmacol. Appl. Skin Physiol. |volume=11 |issue=6 |pages=310–20 |year=1998 |pmid=10343202 |doi= 10.1159/000029854|url=http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=sph11310}}</ref> The PPOX gene makes a membrane bound [[mitochondria]]l enzyme called [[protoporphyrinogen oxidase]], which is critical to the chemical process that leads to heme production. The activity of this enzyme is reduced by 50 percent in most people with variegate porphyria. In severe cases that begin early in life, the enzyme is almost completely inactive. Nongenetic factors such as certain drugs, stress, and others listed above can increase the demand for heme and the enzymes required to make heme. The combination of this increased demand and reduced activity of [[protoporphyrinogen oxidase]] disrupts heme production and allows byproducts of the process to accumulate in the liver, triggering an acute attack.
===Cutaneous Symptoms===
* [[Photosensitivity]]: Patients may develop blistering skin lesions on sun-exposed areas.
* [[Hyperpigmentation]] and [[hypopigmentation]]: Changes in skin color may occur.
* [[Scarring]]: Healing of skin lesions can lead to scarring and changes in skin texture.


Variegate porphyria is inherited in an [[autosomal dominant]] pattern, which means the defective gene is located on an [[autosome]], and inheriting one copy of the defective gene from an affected parent is sufficient to cause the disorder. More severe cases result from inheriting two copies of the defective gene.
===Neurological Symptoms===
 
* [[Abdominal pain]]: Severe, recurrent abdominal pain is a common symptom.
The entire PPOX gene has about 8kb with 13 exon sequences.  It was successfully cloned from a cDNA library in 1995 revealing that, after processing, it is 477 [[nucleotide]]s long.  It has previously been thought that the PPOX gene was located on human [[chromosome 14]],<ref name="pmid3261272">{{cite journal  |vauthors=Bissbort S, Hitzeroth HW, du Wentzel DP, etal |title=Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14 |journal=Hum. Genet. |volume=79 |issue=3 |pages=289–90 |date=July 1988 |pmid=3261272 |doi= 10.1007/BF00366255|url=}}</ref> however mapping experiments (FISH) have shown that it is near 1q23.<ref name="pmid8634714">{{cite journal  |vauthors=Roberts AG, Whatley SD, Daniels J, etal |title=Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23 |journal=Hum. Mol. Genet. |volume=4 |issue=12 |pages=2387–90 |date=December 1995 |pmid=8634714 |doi= 10.1093/hmg/4.12.2387|url=http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=8634714}}</ref>  An additional aggravating mutation affecting  variegate porphyria can be found at 6p21.3 on the [[HFE (gene)|HFE]] gene.<ref name="pmid10401000">{{cite journal |vauthors=de Villiers JN, Hillermann R, Loubser L, Kotze MJ |title=Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria |journal=Hum. Mol. Genet. |volume=8 |issue=8 |pages=1517–22 |date=August 1999 |pmid=10401000 |doi= 10.1093/hmg/8.8.1517|url=http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10401000|doi-access=free }}</ref>
* [[Peripheral neuropathy]]: Patients may experience numbness, tingling, or weakness in the limbs.
 
* [[Seizures]]: Some individuals may have seizures as part of the neurological manifestations.
A 2006 clinical, biochemical and mutational study of eight Swiss variegate porphyria patients and their families found four novel PPOX gene mutations believed to be unique to the Swiss population.<ref name="pmid16947091">{{cite journal |vauthors=Schneider-Yin X, Minder EI |title=Swiss patients with variegate porphyria have unique mutations |journal=Swiss Med Wkly |volume=136 |issue=31–32 |pages=515–9 |date=August 2006 |pmid=16947091 |url=http://www.smw.ch/dfe/set_archiv.asp?target=2006/31/smw-11472 |archive-url=https://archive.today/20130115190232/http://www.smw.ch/dfe/set_archiv.asp?target=2006/31/smw-11472 |url-status=dead |archive-date=2013-01-15 }}</ref>
* [[Psychiatric symptoms]]: These can include anxiety, depression, and hallucinations.


==Diagnosis==
==Diagnosis==
Diagnosis is by finding raised urine porphyrins, raised faecal porphyrins, markedly raised plasma porphyrins (pathognomic) and finding photosensitive cutaneous lesions on clinical examination.
The diagnosis of variegate porphyria is based on clinical presentation, family history, and laboratory tests. Key diagnostic tests include:
* Measurement of porphyrins and their precursors in urine, blood, and stool.
* Genetic testing to identify mutations in the PPOX gene.


==Treatment==
==Management==
[[Liver transplant]] has been used in the treatment of this condition.<ref name="pmid15237381">{{cite journal  |vauthors=Stojeba N, Meyer C, Jeanpierre C, etal |title=Recovery from a variegate porphyria by a liver transplantation |journal=Liver Transpl. |volume=10 |issue=7 |pages=935–8 |date=July 2004 |pmid=15237381 |doi=10.1002/lt.20136}}</ref>
Management of variegate porphyria involves avoiding triggers, managing symptoms, and preventing complications. Key strategies include:
* Avoidance of [[sun exposure]] to prevent cutaneous symptoms.
* Avoidance of drugs and substances known to precipitate attacks, such as certain [[barbiturates]], [[sulfonamides]], and [[alcohol]].
* Use of [[beta-carotene]] supplements to reduce photosensitivity.
* [[Hematin]] infusions during acute attacks to reduce the production of porphyrin precursors.


==Epidemiology==
==Prognosis==
In [[South Africa]], the prevalence of variegate porphyria is approximately 1 in 300.<ref name=Hann2006>{{Cite book  | last1 = Arceci | first1 = Robert. | last2 = Hann | first2 = Ian M. | last3 = Smith | first3 = Owen P. | title = Pediatric hematolog | year = 2006 | publisher = Blackwell Pub. | location = Malden, Mass. | isbn = 978-1-4051-3400-2 | pages =  }}</ref> In Finland, the prevalence is approximately 1 in 75,000.<ref>{{Cite journal | last1 = Mustajoki | first1 = P. | title = Variegate porphyria. Twelve years' experience in Finland | journal = The Quarterly Journal of Medicine | volume = 49 | issue = 194 | pages = 191–203 | year = 1980 | pmid = 7433635}}</ref>
The prognosis for individuals with variegate porphyria varies. With appropriate management, many individuals can lead normal lives. However, severe attacks can be life-threatening and require prompt medical attention.


It is also found in [[Argentina]],<ref name="pmid18570668">{{cite journal |vauthors=Rossetti MV, Granata BX, Giudice J, Parera VE, Batlle A |title=Genetic and biochemical studies in Argentinean patients with variegate porphyria |journal=BMC Med. Genet. |volume=9|pages=54 |year=2008 |pmid=18570668 |pmc=2467414 |doi=10.1186/1471-2350-9-54 }}</ref>  [[Sweden]],<ref name="pmid12859407">{{cite journal |vauthors=Wiman A, Harper P, Floderus Y |title=Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria |journal=Clin. Genet. |volume=64 |issue=2 |pages=122–30 |date=August 2003 |pmid=12859407 |doi=10.1034/j.1399-0004.2003.00116.x }}</ref> and [[Australia]].<ref>{{cite journal|title= Variegate porphyria in Western Australian Aboriginal patients| journal=Internal Medicine Journal|volume = 32 |issue = 9–10 |pages = 445–450 |date=September 2002 |pmid=12380696 |author=Rossi E, Chin CY, Beilby JP, Waso HF, Warnich L |doi=10.1046/j.1445-5994.2002.00274.x}}</ref>
==Related pages==
 
* [[Porphyria]]
==References==
* [[Heme]]
{{Reflist}}
* [[Photosensitivity]]
 
* [[Peripheral neuropathy]]
''This article incorporates public domain text from [http://ghr.nlm.nih.gov The U.S. National Library of Medicine]''


== External links ==
== External links ==
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}}
* {{RareDiseases|7848|Variegate porphyria}}
* {{RareDiseases|7848|Variegate porphyria}}
{{Heme metabolism disorders}}
{{Heme metabolism disorders}}
[[Category:Skin conditions resulting from errors in metabolism]]
[[Category:Skin conditions resulting from errors in metabolism]]
[[Category:Porphyrias]]
[[Category:Porphyrias]]
[[Category:Autosomal dominant disorders]]
[[Category:Autosomal dominant disorders]]
{{stb}}
{{stub}}
[[Category:Porphyrias]]
[[Category:Autosomal dominant disorders]]
[[Category:Metabolic disorders]]

Latest revision as of 03:22, 24 March 2025

A type of porphyria affecting the skin and nervous system



Variegate porphyria
Synonyms Mixed hepatic porphyria
Pronounce
Field Dermatology, Medical genetics, Hepatology
Symptoms Skin photosensitivity, blistering on sun-exposed areas, abdominal pain, neuropathy, seizures, muscle weakness
Complications Liver damage, kidney disease, neurological deficits, skin infections
Onset Typically adolescence or adulthood
Duration Chronic, lifelong condition
Types Hepatic porphyria
Causes Mutations in the PPOX gene affecting protoporphyrinogen oxidase
Risks Family history, certain medications, fasting, hormonal changes, alcohol, smoking, stress
Diagnosis Urine test, plasma fluorescence scan, genetic testing, porphyrin studies
Differential diagnosis Acute intermittent porphyria, porphyria cutanea tarda, erythropoietic protoporphyria
Prevention Avoidance of triggers such as alcohol, sunlight, certain drugs, and fasting
Treatment Symptomatic treatment, liver transplant in severe cases, avoid triggering factors
Medication Hemin (for acute attacks), pain relievers, anti-nausea medications
Prognosis Variable; generally manageable with lifestyle modifications, but attacks can be severe
Frequency Rare; more prevalent in South African populations due to founder effect
Deaths Rare, mostly due to complications during acute attacks if untreated


Variegate porphyria has an autosomal dominant pattern of inheritance.

Variegate porphyria (VP) is a type of porphyria, a group of rare metabolic disorders resulting from a deficiency of enzymes in the heme biosynthesis pathway. This condition is characterized by a combination of cutaneous and neurological symptoms due to the accumulation of porphyrins and their precursors.

Pathophysiology[edit]

Variegate porphyria is caused by a deficiency of the enzyme protoporphyrinogen oxidase (PPOX), which is the seventh enzyme in the heme biosynthetic pathway. This deficiency leads to the accumulation of porphyrins and their precursors, particularly in the liver, resulting in the clinical manifestations of the disease.

Genetics[edit]

Variegate porphyria is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene in each cell is sufficient to cause the disorder. The gene responsible for VP is located on chromosome 1 and is known as the PPOX gene. Mutations in this gene reduce the activity of the protoporphyrinogen oxidase enzyme.

Clinical Features[edit]

The clinical presentation of variegate porphyria can vary widely among affected individuals. The main features include:

Cutaneous Symptoms[edit]

Neurological Symptoms[edit]

  • Abdominal pain: Severe, recurrent abdominal pain is a common symptom.
  • Peripheral neuropathy: Patients may experience numbness, tingling, or weakness in the limbs.
  • Seizures: Some individuals may have seizures as part of the neurological manifestations.
  • Psychiatric symptoms: These can include anxiety, depression, and hallucinations.

Diagnosis[edit]

The diagnosis of variegate porphyria is based on clinical presentation, family history, and laboratory tests. Key diagnostic tests include:

  • Measurement of porphyrins and their precursors in urine, blood, and stool.
  • Genetic testing to identify mutations in the PPOX gene.

Management[edit]

Management of variegate porphyria involves avoiding triggers, managing symptoms, and preventing complications. Key strategies include:

  • Avoidance of sun exposure to prevent cutaneous symptoms.
  • Avoidance of drugs and substances known to precipitate attacks, such as certain barbiturates, sulfonamides, and alcohol.
  • Use of beta-carotene supplements to reduce photosensitivity.
  • Hematin infusions during acute attacks to reduce the production of porphyrin precursors.

Prognosis[edit]

The prognosis for individuals with variegate porphyria varies. With appropriate management, many individuals can lead normal lives. However, severe attacks can be life-threatening and require prompt medical attention.

Related pages[edit]

External links[edit]


Heme metabolism disorders
Porphyria,
hepatic and erythropoietic
(porphyrin)
Hereditary hyperbilirubinemia
(bilirubin)
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