Editing Porphyria (section)

==Signs and symptoms==
{{More citations needed section|date = January 2016}}
[[File:Prfr1.jpg|thumb|A skin rash in a person with porphyria]]

===Acute porphyrias===
[[Acute intermittent porphyria]] (AIP), [[variegate porphyria]] (VP), [[aminolevulinic acid dehydratase deficiency porphyria]] (ALAD) and [[hereditary coproporphyria]] (HCP). These diseases primarily affect the [[nervous system]], resulting in episodic crises known as acute attacks. The major symptom of an acute attack is [[abdominal pain]], often accompanied by [[vomiting]], [[hypertension]] (elevated blood pressure), and [[tachycardia]] (an abnormally rapid heart rate).<ref name=Stein2017/>

The most severe episodes may involve neurological complications: typically motor neuropathy (severe dysfunction of the peripheral nerves that innervate muscle), which leads to muscle weakness and potentially to [[Tetraplegia|quadriplegia]] (paralysis of all four limbs) and [[central nervous system]] symptoms such as [[seizure]]s and [[coma]]. Occasionally, there may be short-lived psychiatric symptoms such as anxiety, confusion, [[hallucination]]s, and, very rarely, overt psychosis. All these symptoms resolve once the acute attack passes.{{citation needed|date=March 2021}}

Given the many presentations and the relatively low occurrence of porphyria, patients may initially be suspected to have other, unrelated conditions. For instance, the polyneuropathy of acute porphyria may be mistaken for [[Guillain–Barré syndrome]], and porphyria testing is commonly recommended in those situations.<ref>{{cite journal |vauthors=Albers JW, Fink JK |title = Porphyric neuropathy |journal = Muscle Nerve |volume = 30 |issue = 4 |pages = 410–422 |year = 2004 |pmid = 15372536 |doi = 10.1002/mus.20137 |hdl = 2027.42/34640 |s2cid = 68067335 |url = https://deepblue.lib.umich.edu/bitstream/2027.42/34640/1/20137_ftp.pdf |hdl-access = free }}</ref> Elevation of aminolevulinic acid from lead-induced disruption of heme synthesis results in lead poisoning having symptoms similar to acute porphyria.<ref>{{cite book |last=Vannotti |first=Alfred |name-list-style = vanc |date=1954 |title=Porphyrins: Their Biological and Chemical Importance |url=https://books.google.com/books?id=-bzoAAAAIAAJ |publisher=Hilger & Watts, Hilger Division |page=126 |quote=Indeed, lead poisoning, like all porphyrin diseases, is accompanied by obstinate constipation, nervous lesions, hyperpigmentation and abdominal attacks.}}</ref><ref>{{cite book|last1=Dancygier|first1=Henryk |name-list-style = vanc |title=Clinical Hepatology: Principles and Practice of Hepatobiliary Diseases|date=2009|publisher=Springer Science & Business Media|isbn=9783642045196|page=1088|url=https://books.google.com/books?id=lrPX8C4p90QC&pg=PA1088|url-status=live|archive-url=https://web.archive.org/web/20170908185104/https://books.google.com/books?id=lrPX8C4p90QC&pg=PA1088|archive-date=8 September 2017|df=dmy-all}}</ref><ref>{{cite journal | vauthors = Akshatha LN, Rukmini MS, Mamatha TS, Sadashiva Rao P, Prashanth B | title = Lead poisoning mimicking acute porphyria! | journal = Journal of Clinical and Diagnostic Research | volume = 8 | issue = 12 | pages = CD01-2 | date = December 2014 | pmid = 25653942 | pmc = 4316248 | doi = 10.7860/JCDR/2014/10597.5315}}</ref><ref>{{cite journal | vauthors = Tsai MT, Huang SY, Cheng SY | title = Lead Poisoning Can Be Easily Misdiagnosed as Acute Porphyria and Nonspecific Abdominal Pain | journal = Case Reports in Emergency Medicine | volume = 2017 | pages = 9050713 | date = 2017 | pmid = 28630774 | pmc = 5467293 | doi = 10.1155/2017/9050713| doi-access = free }}</ref><ref>{{cite journal | title = Hereditary Coproporphyria | journal = GeneReviews | date = 2018 | pmid = 23236641 | url = https://www.ncbi.nlm.nih.gov/books/NBK114807/ | access-date = 28 February 2020 | quote = the symptoms in lead poisoning closely mimic those of acute porphyria | last1 = Wang | first1 = B. | last2 = Bissell | first2 = D. M. | last3 = Adam | first3 = M. P. | last4 = Ardinger | first4 = H. H. | last5 = Pagon | first5 = R. A. | last6 = Wallace | first6 = S. E. | author7 = Bean LJH | last8 = Stephens | first8 = K. | last9 = Amemiya | first9 = A.}}</ref><ref>{{cite news |last=Murphy |first=Brian |date=3 November 2020 |title=What Tests Can Help Diagnose Porphyria? |url=https://porphyrianews.com/2020/11/03/what-tests-can-help-diagnose-porphyria/ |work= |access-date=22 May 2021}}</ref>

===Chronic porphyrias===
The non-acute porphyrias are X-linked dominant protoporphyria (XLDPP), congenital [[erythropoietic porphyria]] (CEP), [[porphyria cutanea tarda]] (PCT), and [[erythropoietic protoporphyria]] (EPP). None of these is associated with acute attacks: their primary manifestation is with skin disease. For this reason, these four porphyrias—along with two acute porphyrias, VP and HCP, that may also involve skin manifestations—are sometimes called cutaneous porphyrias.

Skin disease is encountered where excess porphyrins accumulate in the skin. Porphyrins are photoactive molecules, and exposure to light results in promotion of electrons to higher energy levels. When these return to the resting energy level or ground state, energy is released. This accounts for the property of fluorescence typical of the porphyrins. This causes local skin damage.

Two distinct patterns of skin disease are seen in porphyria:
* '''Immediate photosensitivity.''' This is typical of XLDPP and EPP. Following a variable period of [[Health effects of sunlight exposure|sun exposure]]—typically about 30 minutes—patients complain of severe pain, burning, and discomfort in exposed areas. Typically, the effects are not visible, though occasionally there may be some redness and swelling of the skin.
* '''Vesiculo-erosive skin disease.''' This—a reference to the characteristic [[blister]]ing (vesicles) and open sores (erosions) noted in patients—is the pattern seen in CEP, PCT, VP, and HCP. The changes are noted only in sun-exposed areas such as the face and back of the hands. Milder skin disease, such as that seen in VP and HCP, consists of increased skin fragility in exposed areas with a tendency to form blisters and erosions, particularly after minor knocks or scrapes. These heal slowly, often leaving small scars that may be lighter or darker than normal skin. More severe skin disease is sometimes seen in PCT, with prominent lesions, darkening of exposed skin such as the face, and [[hypertrichosis]]: abnormal hair growth on the face, particularly the cheeks. The most severe disease is seen in CEP and a rare variant of PCT known as [[hepatoerythropoietic porphyria]] (HEP); symptoms include severe shortening of digits, loss of skin appendages such as hair and nails, and severe scarring of the skin with progressive disappearance of ears, lips, and nose. Patients may also show deformed, discolored teeth or gum and eye abnormalities.

===Congenital porphyrias===
* Congenital porphyrias are genetic disorders caused by mutations in enzymes involved in the heme biosynthesis pathway. There are several types of congenital porphyrias, including erythropoietic protoporphyria (EPP), congenital erythropoietic porphyria (CEP), and porphyria cutanea tarda (PCT). Each type is characterized by specific enzyme deficiencies leading to the accumulation of different porphyrins.
* Erythropoietic protoporphyria (EPP) is caused by a deficiency in ferrochelatase, leading to the accumulation of protoporphyrin IX in red blood cells, plasma, and tissues. Patients with EPP experience severe photosensitivity, with exposure to sunlight causing painful skin reactions.
* Congenital erythropoietic porphyria (CEP), also known as Günther's disease, results from a deficiency in uroporphyrinogen III synthase. This leads to the accumulation of uroporphyrin I and coproporphyrin I in the bone marrow, blood, and urine. Symptoms of CEP include severe photosensitivity, anemia, splenomegaly, and often disfiguring cutaneous lesions.
* Diagnosis of congenital porphyrias involves clinical evaluation, biochemical testing, and genetic analysis. Treatment aims to manage symptoms and prevent acute attacks by avoiding triggers, such as sunlight exposure, certain medications, and alcohol. Additionally, treatments may include phlebotomy to reduce iron levels in PCT, administration of heme preparations to alleviate symptoms, and liver transplantation in severe cases. Early diagnosis and appropriate management are crucial in improving the quality of life for individuals with congenital porphyrias.