Editing Porphyria (section)

==Cause==
The porphyrias are generally considered genetic in nature.{{citation needed|date=July 2020}}

===Genetics===
Subtypes of porphyrias depend on which enzyme is deficient.

{| class="wikitable"
!Porphyria type
!Deficient [[enzyme]]
!Type of porphyria
!Inheritance
!Symptoms
![[Prevalence]]
|-
| [[Aminolevulinate dehydratase deficiency porphyria]] (ALADP)
| [[5-aminolevulinate dehydratase]] (ALAD)
| Hepatic
| [[Autosomal recessive]]<ref name=brschemi18-1>Table 18-1 in: {{Cite book |author1=Marks, Dawn B. |author2=Swanson, Todd |author3=Sandra I Kim |author4=Marc Glucksman |title=Biochemistry and molecular biology |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |year=2007 |isbn=978-0-7817-8624-9 |url-access=registration |url=https://archive.org/details/biochemistrymole0000swan_f9p0 }}</ref>
| Abdominal pain, neuropathy<ref name=brschemi18-1/>
| Extremely rare; fewer than 10 cases ever reported.<ref name=RD>[http://rarediseasesnetwork.epi.usf.edu/porphyrias/patients/ADP/ Overview of the Porphyrias] {{webarchive|url=https://web.archive.org/web/20110722233132/http://rarediseasesnetwork.epi.usf.edu/porphyrias/patients/ADP/ |date=22 July 2011 }} at The Porphyrias Consortium (a part of NIH Rare Diseases Clinical Research Network (RDCRN)) Retrieved June 2011</ref>
|-
| [[Acute intermittent porphyria]] (AIP)
| [[Hydroxymethylbilane synthase]] (HMBS) formerly porphobilinogen deaminase (PBGD)
| Hepatic
| [[Autosomal dominant]]<ref name=brschemi18-1/>
| Periodic abdominal pain, [[peripheral neuropathy]], psychiatric disorders, tachycardia<ref name=brschemi18-1/>
| 1 in 10,000<ref name=medscape/>–20,000<ref name=medscape>[http://emedicine.medscape.com/article/1148341-overview#a0199 Medscape - Diseases of Tetrapyrrole Metabolism - Refsum Disease and the Hepatic Porphyrias ] {{webarchive|url=https://web.archive.org/web/20110604065657/http://emedicine.medscape.com/article/1148341-overview |date=4 June 2011 }} Author: Norman C Reynolds. Chief Editor: Stephen A Berman. Updated: 23 March 2009</ref>
|-
| [[Congenital erythropoietic porphyria]] (CEP)
| [[Uroporphyrinogen III synthase|uroporphyrinogen synthase (UROS)]]
| Erythropoietic
| [[Autosomal recessive]]<ref name=brschemi18-1/>
| Severe photosensitivity with erythema, swelling and blistering. Hemolytic anemia, [[splenomegaly]]<ref name=brschemi18-1/>
| 1 in 1,000,000 or less.<ref name="Thadani"/>
|-
| [[Porphyria cutanea tarda]] (PCT)
| [[Uroporphyrinogen III decarboxylase|uroporphyrinogen decarboxylase (UROD)]]
| Hepatic
| Approximately 80% sporadic,<ref>{{cite web |title=OMIM Entry - 176090 - PORPHYRIA CUTANEA TARDA, TYPE I |url=https://omim.org/entry/176090 |website=omim.org |access-date=24 February 2021 |language=en-us}}</ref> 20% [[Autosomal dominant]]<ref name=brschemi18-1/>
| Photosensitivity with [[Vesicle (dermatology)|vesicles]] and [[Bulla (dermatology)|bullae]]<ref name=brschemi18-1/>
| 1 in 10,000<ref name=Hann2006/>
|-
| [[Hereditary coproporphyria]] (HCP)
| [[Coproporphyrinogen III oxidase|coproporphyrinogen oxidase (CPOX)]]
| Hepatic
| [[Autosomal dominant]]<ref name=brschemi18-1/>
| Photosensitivity, neurologic symptoms, [[colic]]<ref name=brschemi18-1/>
| 1 in 500,000<ref name=Hann2006/>
|-
| [[Harderoporphyria]]
| [[Coproporphyrinogen III oxidase|coproporphyrinogen oxidase (CPOX)]]
| Erythropoietic
| [[Autosomal recessive]]<ref name=brschemi18-1/>
| Jaundice, anemia, enlarged liver and spleen, often neonatal. Photosensitivity later.
| Extremely rare; fewer than 10 cases ever reported.
|-
| [[Variegate porphyria]] (VP)
| [[Protoporphyrinogen oxidase|protoporphyrinogen oxidase (PPOX)]]
| Hepatic
| [[Autosomal dominant]]<ref name=VPNBK>{{cite journal|last1=Singal|first1=AK|last2=Anderson|first2=KE|last3=Pagon|first3=RA|last4=Adam|first4=MP|last5=Ardinger|first5=HH|last6=Wallace|first6=SE|last7=Amemiya|first7=A|last8=Bean|first8=LJH|last9=Bird|first9=TD|last10=Dolan|first10=CR|last11=Fong|first11=CT|last12=Smith|first12=RJH|last13=Stephens|first13=K|title=Variegate Porphyria|journal=GeneReviews|date=2013|pmid=23409300|url=https://www.ncbi.nlm.nih.gov/books/NBK121283/|access-date=18 April 2015|publisher=University of Washington|location=Seattle, USA|url-status=live|archive-url=https://web.archive.org/web/20170118123846/https://www.ncbi.nlm.nih.gov/books/NBK121283/|archive-date=18 January 2017|df=dmy-all}}</ref>
| Photosensitivity, neurologic symptoms, developmental delay
| 1 in 300 in South Africa<ref name=Hann2006/><br />1 in 75,000 in Finland<ref>{{cite journal | author = Mustajoki 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>
|-
| [[Erythropoietic protoporphyria]] (EPP)
| [[ferrochelatase]] (FECH)
| Erythropoietic
| [[Autosomal recessive]]<ref name=brschemi18-1/>
| Photosensitivity with skin lesions. Gallstones, mild liver dysfunction<ref name=brschemi18-1/>
| 1 in 75,000<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 }}</ref>–200,000<ref name=Hann2006/>
|-
|}

[[X-linked dominant inheritance|X-linked dominant]] protoporphyria is a rare form of [[erythropoietic protoporphyria]] caused by a gain-of-function [[mutation]] in [[ALAS2]] characterized by severe [[photosensitivity in humans|photosensitivity]].<ref>{{cite web |title=OMIM Entry - # 300752 - PROTOPORPHYRIA, ERYTHROPOIETIC, X-LINKED; XLEPP |url=https://omim.org/entry/300752 |website=omim.org |language=en-us}}</ref><ref>{{cite web |title=Orphanet: X linked erythropoietic protoporphyria |url=https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=443197 |website=www.orpha.net}}</ref>

In the autosomal recessive types, anyone who inherit a single gene may become a carrier. Generally they do not have symptoms but may pass the gene on to offspring.<ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066|title=Porphyria - Symptoms and causes|website=Mayo Clinic|language=en|access-date=2020-03-05}}</ref>

===Triggers===
Acute porphyria can be triggered by a number of drugs, most of which are believed to trigger it by interacting with enzymes in the liver that are made with heme. Such drugs include:<ref name=APF>{{cite web|title=About Porphyria: Safety database|work=Porphyria Drug Safety Database|publisher=American Porphyria Foundation|access-date=27 August 2017|author=Tishler, PV|url=http://www.porphyriafoundation.com/drug_database/|url-status=dead|archive-url=https://web.archive.org/web/20170712121843/http://www.porphyriafoundation.com/drug_database/|archive-date=12 July 2017|df=dmy-all}}</ref><ref name=EPN>{{cite web|title=napos|work=The Drug Database for Acute Porphyria|publisher=European Porphyria Network|access-date=27 August 2017|author=Brun, A|url=http://www.drugs-porphyria.org|url-status=dead|archive-url=https://web.archive.org/web/20170823070041/http://www.drugs-porphyria.org/|archive-date=23 August 2017|df=dmy-all}}</ref><ref name=BNF>{{cite book | author = Joint Formulary Committee | title = British National Formulary (BNF) | year = 2013 | url = https://archive.org/details/bnf65britishnati0000unse/page/663 | isbn = 978-0-85711-084-8 | edition = 65 | location = London, UK | publisher = Pharmaceutical Press | page = [https://archive.org/details/bnf65britishnati0000unse/page/663 663] }}</ref>
* [[Sulfonamide]]s, including [[sulfadiazine]], [[sulfasalazine]] and [[trimethoprim/sulfamethoxazole]].
* [[Sulfonylurea]]s like [[glibenclamide]], [[gliclazide]] and [[glimepiride]], although [[glipizide]] is thought to be safe.
* [[Barbiturates]] including [[thiopental]], [[phenobarbital]], [[primidone]], etc.
* Systemic treatment with [[antifungals]] including [[fluconazole]], [[griseofulvin]], [[ketoconazole]] and [[voriconazole]]. (Topical use of these agents is thought to be safe due to minimal systemic absorption.)
* Certain [[antibiotics]] like [[rifapentine]], [[rifampicin]], [[rifabutine]], [[isoniazid]], [[nitrofurantoin]] and, possibly, [[metronidazole]].
* [[Ergot]] derivatives including [[dihydroergotamine]], [[ergometrine]], [[ergotamine]], [[methysergide]], etc.
* Certain [[antiretroviral]] medications ( [[indinavir]], [[nevirapine]], [[ritonavir]], [[saquinavir]], etc.)
* [[Progestogen]]s
* Some [[anticonvulsants]] including: [[carbamazepine]], [[ethosuximide]], [[phenytoin]], [[topiramate]], [[valproate]].
* Some [[analgesics|painkillers]] like [[dextropropoxyphene]], [[ketorolac]], [[metamizole]], [[pentazocine]]
* Some cancer treatments like [[bexarotene]], [[busulfan]], [[chlorambucil]], [[estramustine]], [[etoposide]], [[flutamide]], [[idarubicin]], [[ifosfamide]], [[irinotecan]], [[ixabepilone]], [[letrozole]], [[lomustine]], [[megestrol]], [[mitomycin]], [[mitoxantrone]], [[paclitaxel]], [[procarbazine]], [[tamoxifen]], [[topotecan]]
* Some [[antidepressants]] like [[imipramine]], [[phenelzine]], [[trazodone]]
* Some [[antipsychotics]] like [[risperidone]], [[ziprasidone]]
* Some [[retinoids]] used for skin conditions like [[acitretin]] and [[isotretinoin]]
* Miscellaneous others including: [[cocaine]], [[methyldopa]], [[fenfluramine]], [[disulfiram]], [[orphenadrine]], [[pentoxifylline]], and [[sodium aurothiomalate]].