Together with hereditary coproporphyria (HCP), acute intermittent porphyria (AIP), and δ-aminolevulinic acid dehydratase porphyria (ADP), variegate porphyria (VP) belongs to the group of acute hepatic porphyrias, as mitochondrial protoporphyrin oxidase (PPOX), the enzyme affected in VP and necessary for the seventh step in heme synthesis, performs its respective function of converting protoporphyrinogen IX to protoporphyrin IX in the liver [1] [2]. In VP, autosomal dominant gene mutations of the PPOX lead to its insufficient activity and the onset of cutaneous and neurovisceral symptoms [1] [2] [3]. Chronic blistering lesions in the form of erosions, bullae, and ulcerations with crusting and slow recovery are principal manifestations on the skin [2] [4]. Lesions are usually seen in childhood on the hands and face [2] [4]. The trauma of the skin that is exposed to sunlight seems to be the major risk factor for their appearance [4] [5]. Hypertrichosis and either hyper or hypopigmentation, as well as thickening of the skin are other notable findings [2]. On the other hand, vomiting, constipation, tachycardia, fever, fatigue, abdominal pain, muscle weakness, seizures, mental instability, paresis and neuromuscular deficits are hallmarks of an "acute neurovisceral attack" that is typical for patients suffering from VP [2] [3] [4]. Due to the fact that respiratory paralysis is a known complication, but also because the diagnosis is often delayed, a 10% mortality rate from acute attacks is observed [2] [6]. Patients may exhibit either of the two types of symptoms or both, whereas growth retardation and significant developmental disturbances are seen in the rare homozygous forms of VP [5].

• Weakness

  Weakness of limbs, tremor of the legs while walking and brachydactyly were the other findings in this case. [ijponline.biomedcentral.com]

  Neurological manifestations include muscle and limb weakness that may progress to areflexic quadriparesis (weak arms and legs), seizures, and mental changes such as anxiety and hallucinations. [dermnetnz.org]

  Later, she developed progressively generalized muscle weakness of hands and legs with tingling sensation within one week. Physical exam revealed moderate distal muscle weakness with impaired sensation, but no skin lesion. [neurology.org]

  Muscle weakness, seizures, and increased heart rate and blood pressure may also occur. [rarediseases.info.nih.gov]

• Abdominal Pain

  After the surgical cure of abdominal hernia and appendagitis healing, abdominal pain disappeared. However, severe fatigue persisted in addition to limb neuropathic pain and preexisting low back pain, preventing the patient from returning to work. [frontiersin.org]

  During the examination, only the diffuse abdominal pain without accompanying signs of peritonism was relevant. [revespcardiol.org]

  The congenital form is more serious, resulting in crises of acute abdominal pain and certain neurological complications. [medical-dictionary.thefreedictionary.com]

  VP usually presents in post-pubertal age with attacks of abdominal pain, skin manifestations, neurological as well as psychiatric disturbances [1,2]. [cureus.com]

  Increased sympathetic activity may also have caused intussusception and focal renal vasoconstriction, both of which may be underdiagnosed causes of abdominal pain in acute porphyria. [ncbi.nlm.nih.gov]

• Vomiting

  Common neurological symptoms include abdominal pain, nausea, vomiting, constipation, extremity pain and weakness, anxiety, restlessness and convulsions. [porphyriafoundation.org]

  Systemic symptoms Acute attacks cause severe abdominal pain, uncontrolled vomiting, diarrhoea and constipation. [dermnetnz.org]

  People with variegate porphyria can also have neurological symptoms in the form of episodes (acute attacks) of severe stomach pain, nausea and vomiting. [1] [2] Symptoms usually begin in adulthood. [rarediseases.info.nih.gov]

• Constipation

  She was admitted in an acute attack and developed severe dysautonomia manifested clinically by postural hypotension, tachycardia and constipation with severe abdominal pain. [ncbi.nlm.nih.gov]

  Common neurological symptoms include abdominal pain, nausea, vomiting, constipation, extremity pain and weakness, anxiety, restlessness and convulsions. [porphyriafoundation.org]

  Common symptoms include cutaneous photosensitivity, abdominal pain, constipation, nausea, vomiting, hypertension, tachycardia, neuropathy and back pain. Disorientation and frank psychosis may be conspicuous features of VP. [themedicalbiochemistrypage.org]

• Nausea

  Common neurological symptoms include abdominal pain, nausea, vomiting, constipation, extremity pain and weakness, anxiety, restlessness and convulsions. [porphyriafoundation.org]

  Nausea and vomiting can be treated with ondansetron or a comparable medicine, while nausea, agitation, and hallucinations can be treated with phenothiazines. [news-medical.net]

• Abdominal Cramps

  Masters suggested Ryan's abdominal bleeding might be caused by acute intermittent porphyria, but there were no abdominal cramps to go along with it. [house.wikia.com]

  Symptoms present as an acute attack, often as severe abdominal cramping with vomiting and constipation. Acute intermittent porphyria Acute intermittent porphyria (AIP) is a deficiency of the enzyme hydroxymethylbilane synthase (HMBS). [healthline.com]

• Hypertension

  The trigger in our case was probably hypertension. In our literature review we found no reported case of PRES as a complication of VP. [cureus.com]

  Papers PDF Open Access More filters Journal Article•DOI• TL;DR: Patients with AIP or VP showed increased incidences of hepatocellular carcinoma, and probably also chronic renal failure and hypertension and hypertension. ...read moreread less Abstract: [typeset.io]

  […] porphyria (VP), a low-penetrant autosomal dominant inherited disorder of haem metabolism, is characterised by photosensitivity (Fig. 1) and a propensity to develop acute neuropsychiatric attacks with abdominal pain, vomiting, constipation, tachycardia, hypertension [ncbi.nlm.nih.gov]

  Common symptoms include cutaneous photosensitivity, abdominal pain, constipation, nausea, vomiting, hypertension, tachycardia, neuropathy and back pain. Disorientation and frank psychosis may be conspicuous features of VP. [themedicalbiochemistrypage.org]

  It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. [uniprot.org]

• Tachycardia

  She was admitted in an acute attack and developed severe dysautonomia manifested clinically by postural hypotension, tachycardia and constipation with severe abdominal pain. [ncbi.nlm.nih.gov]

  Common symptoms include cutaneous photosensitivity, abdominal pain, constipation, nausea, vomiting, hypertension, tachycardia, neuropathy and back pain. Disorientation and frank psychosis may be conspicuous features of VP. [themedicalbiochemistrypage.org]

  It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. [uniprot.org]

  On the other hand, vomiting, constipation, tachycardia, fever, fatigue, abdominal pain, muscle weakness, seizures, mental instability, paresis and neuromuscular deficits are hallmarks of an "acute neurovisceral attack" that is typical for patients suffering [symptoma.com]

• Photosensitivity

  In VP patients, a worsening of photosensitivity can thus be induced due to complications associated with some other disease, thereby affecting their porphyrin-heme biosynthesis. [ncbi.nlm.nih.gov]

  It is an inherited disorder characterised by skin photosensitivity (reaction to light), systemic symptoms arising from neurological problems, or both. [dermnetnz.org]

  Manifestations of porphyria include gastrointestinal, neurologic, and psychologic symptoms, cutaneous photosensitivity, pigmentation of the face (and later of the bones), and anemia with enlargement of the spleen. [medical-dictionary.thefreedictionary.com]

• Blister

  They were advised on the importance of sun protection to avoid triggering skin blisters. [porphyrianews.com]

  Blistering cutaneous porphyrias (including VP). When VP or any other blistering cutaneous porphyria is suspected, the recommended initial test is measurement of plasma or urine porphyrins. [ncbi.nlm.nih.gov]

• Cutaneous Manifestation

  There was no relation between genotype assessed by functional analysis and the presence or severity of non-cutaneous manifestations. The mutations were absent from 104 unrelated patients with autosomal dominant VP. [ncbi.nlm.nih.gov]

• Hyperpigmentation

  He was presented with lesions, hyperpigmentation, fragility, and blistering of sun-exposed skin. The weakness of limbs and brachydactyly were observed. [ijponline.biomedcentral.com]

  It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. [uniprot.org]

  We present the case of two sisters showing cutaneous signs typical of PCT: blisters, photosensitivity, hyperpigmentation, hypertrichosis, cutaneous fragility, and no acute symptomatology. [porphyria.eu]

  Hyperpigmentation and hypertrichosis of the face are possible side effects. Cutaneous manifestations may improve during the winters and be less common in northern areas and those with dark skin. [news-medical.net]

• Skin Rash

  Cutaneous porphyrias This type of porphyria mainly affects the skin, causing skin rashes and other problems. The excess porphyrins that build up can interact with light, making the skin light-sensitive. [patient.info]

  Reactions such as dizziness, feeling faint, allergies or short-lived skin rashes (which may occur immediately or very soon after taking the drug) are common after taking drugs and rarely have anything to do with porphyria. [porphyria.org.uk]

  [ more ] 0008066 Cutaneous photosensitivity Photosensitive skin Photosensitive skin rashes Photosensitivity Sensitivity to sunlight Skin photosensitivity Sun sensitivity [ more ] 0000992 5%-29% of people have these symptoms Abdominal pain Pain in stomach [rarediseases.info.nih.gov]

• Psychiatric Manifestation

  Much the same way as previously diagnosed patients with MCSS showed similarities with somatization disorders, the psychiatric manifestations of acute porphyria may also be confused with various psychiatric disorders (especially when combined with an isolated [clinicaladvisor.com]

  Santosh PJ, Malhotra S: Varied psychiatric manifestations of acute intermittent porphyria. Biol Psychiatry 1994; 36:744-747Crossref, Medline, Google Scholar 36. [ajp.psychiatryonline.org]

  Depression and other chronic psychiatric manifestations may occur, but are usually not attributable to VP, except in patients with frequent recurring attacks and chronic pain [56,63]. Monitoring of such patients for depression is recommended. [medilib.ir]

• Seizure

  He was also admitted to a local hospital and received anti-seizure drug due to episodes of generalized tonic-clonic seizure (GTC). She had also a history of delayed developmental milestones and started walking by 3 years old. [ijponline.biomedcentral.com]

  A 12-year-old pre-pubertal boy already diagnosed with VP presents with seizure, visual disturbance, altered mental status, headache, and hypertension. [cureus.com]

  In acute porphyric attacks, seizures can be treated with intravenous diazepam, levetiracetam or propofol if status epilepticus develops; a single or few seizures may not require antiepileptic drug treatment in the long term, provided the porphyria itself [pn.bmj.com]

  Neurological manifestations include muscle and limb weakness that may progress to areflexic quadriparesis (weak arms and legs), seizures, and mental changes such as anxiety and hallucinations. [dermnetnz.org]

  We delineate a syndrome principally characterized by growth retardation, developmental delay, epileptic seizures, photosensitivity and an abnormal porphyrin excretion pattern. [ncbi.nlm.nih.gov]

• Confusion

  For a long time, this disease has caused confusion among the porphyrias because it presents with clinical symptoms and biochemical findings that can be similar to those found in other types of porphyrias. [ncbi.nlm.nih.gov]

  Confusion, convulsions, and muscular weakness, due to neurologic impairment, may lead to paralysis. An acute attack usually lasts for days or longer. Recovery from severe paralysis is generally slow. [sema4genomics.com]

  The central nervous system is often affected with insomnia, restlessness, agitation, confusion, hallucinations and convulsions. The level of sodium in the blood may decrease and cause convulsions. [porphyriafoundation.org]

  Disorientation Easily confused Mental disorientation [ more ] 0001289 Constipation 0002019 Depressivity Depression 0000716 Motor polyneuropathy 0007178 Muscle weakness Muscular weakness 0001324 Nausea and vomiting 0002017 Seizures Seizure 0001250 Visual [rarediseases.info.nih.gov]

• Neurologic Manifestation

  Variegate porphyria (VP) is an autosomal dominant disease characterized in adults by mechanical fragility and blistering of sun-exposed skin or acute visceral and neurological manifestations. [ncbi.nlm.nih.gov]

  The term “variegate” assigned to this particular porphyria relates to the fact that the disease can present with neurological manifestations, cutaneous photosensitivity or both. [themedicalbiochemistrypage.org]

  Neurological manifestations include muscle and limb weakness that may progress to areflexic quadriparesis (weak arms and legs), seizures, and mental changes such as anxiety and hallucinations. [dermnetnz.org]

  Variegate porphyria (VP) is a type of autosomal dominant hepatic porphyria secondary to protoporphyrinogen oxidase activity deficiency that can present acute neurological manifestations and/or cutaneous photosensitivity. [revespcardiol.org]

• Personality Change

  Those with acute forms of porphyria develop numbness, tingling, paralysis, cramping, vomiting, constipation, personality changes or mental disorders, and/or pain in the abdomen, chest, limbs, or back. [medicinenet.com]

  The imbalance can contribute to some of these symptoms: Abdominal pain, often severe Chest pain Increased heart rate and blood pressure Limb and back pain Muscle weakness Tingling Loss of sensation Cramping Vomiting and constipation Personality changes [webmd.com]

  Personality changes developed along with mood lability, intermittent suicidal ideation, and behavioral dyscontrol. At times he withdrew to his home, exhibiting anhedonia and psychomotor slowness. [ajp.psychiatryonline.org]

• Agitated Delirium

  Clinical Manifestations Reported clinical manifestations of acute porphyria include neuropsychiatric symptoms and clinical signs (hysteria, anxiety, depression, phobias, psychosis, agitation, delirium, restlessness, seizures, neuropathy, sensory involvement [ajp.psychiatryonline.org]

  For an attack requiring hospitalization, opioids, or other intravenous medication, or accompanied by nausea and vomiting, motor neuropathy, paresis, seizures, agitation, delirium, psychosis, ileus that prevents oral intake, or hyponatremia, we recommend [medilib.ir]

• Dark Urine

  The patient recalled passing dark urine after surgery and was subsequently hospitalized for 3 months. [medicaljournals.se]

  In addition, she repeatedly observed that her urines were dark-colored. [frontiersin.org]

  Urine needs to be transported to the laboratory in a container protecting it from light, otherwise false positive results can arise. [health24.com]

  In some forms of porphyria, accumulated heme precursors excreted in the urine may cause various changes in color, after exposure to sunlight, to a dark reddish or dark brown color. Even a purple hue or red urine may be seen. [house.wikia.com]

• Red Urine

  Some signs and symptoms of an acute attack are: pain, red, burning or blistering skin, red urine, neurological changes, or psychological changes. Resources BOOKS Deats-O'Reilly, Diana. Porphyria: The Unknown Disease. [healthofchildren.com]

  In some forms of porphyria, accumulated heme precursors excreted in the urine may cause various changes in color, after exposure to sunlight, to a dark reddish or dark brown color. Even a purple hue or red urine may be seen. [house.wikia.com]

  Porphyrins are substances that represent the building blocks of hemoglobin, the red-colored protein in red blood cells that transport oxygen. [utswmed.org]

Early recognition of VP, particularly when patients develop neurovisceral attacks, can be life-saving, which is why a thorough workup is necessary. The first step is obtaining a detailed patient and family history, given the autosomal dominant nature of the disease. Furthermore, the population of Dutch descendants living in South Africa is at the greatest risk for developing VP due to the founder effect [2] [3] [5]. After history taking, the physical examination, if done properly, could identify typical skin lesions and assess their progression, thus a provisional diagnosis of VP can be made. Laboratory studies are the mainstay in diagnosing porphyrias, and the following tests should be implemented when a suspicion toward VP exists:

• Stool analysis - The levels of protoporphyrin and coproporphyrin in feces are very high during acute attacks, and are one of the most reliable indicators when it comes to identifying VP as the possible cause [2] [6]. However, normal levels are observed during remissions and milder attacks in some patients and the diagnosis can be missed [2] [6].
• Serum and urine testing - If patients present with cutaneous lesions, serum levels of porphyrin might be elevated, whereas the urinary determination of aminolevulinic acid dehydratase (ALA) and porphobilinogen (PBG) may be a useful tool during acute attacks [5]. However, one of the most specific forms of testing is the plasma fluorescence emission spectrum analysis, which reveals a unique fluorescence emission peak at 626 nm in a neutral pH [2] [5] [6].

A definite diagnosis, however, is made after conducting genetic studies on the PPOX gene located on chromosome 1, or by detecting a lower PPOX activity in lymphocytes [4] [5] [6].

• Hyponatremia

  It is very important to monitor patients with hyponatremia because they can develop seizures. [hematologyandoncology.net]

  We hypothesize that brainstem dysfunction in VP patients with a history of porphyric crises may be due to neurotoxic effects of porphyrin precursors as well as subclinical osmolarity changes due to hyponatremia. [ncbi.nlm.nih.gov]

Treatment of Variegate Porphyria Treatment of VP involves a high carbohydrate diet and during a severe attack an infusion of 10% glucose is highly recommended, which is the same recommended intervention in treating acute attacks in the related porphyria [themedicalbiochemistrypage.org]

Types I-III are clinically indistinguishable and respond to the same treatments. 3. 4. [ncbi.nlm.nih.gov]

Prognosis - Variegate porphyria Treatment - Variegate porphyria Liver transplant has been used in the treatment of this condition. Resources - Variegate porphyria Not supplied. [checkorphan.org]

The incidence of serious complications and mortality in this series was low, confirming a trend to an increasingly good prognosis for patients with acute porphyria who receive expert treatment. [ncbi.nlm.nih.gov]

Outlook / Prognosis What is the prognosis (outlook) for people with porphyria? Most people with porphyria recover from their symptoms. Because genetic mutations cause this condition, you may experience symptoms throughout your life. [my.clevelandclinic.org]

The prognosis is usually good if the disease is recognized and treated promptly, before nerve damage develops. Although symptoms usually resolve after an attack, recovery of neuromuscular function (in a severe case) may require several months. [porphyriafoundation.org]

Access More filters Journal Article•DOI• TL;DR: Patients with AIP or VP showed increased incidences of hepatocellular carcinoma, and probably also chronic renal failure and hypertension and hypertension. ...read moreread less Abstract: We evaluated the prognosis [typeset.io]

Inglês : BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications CN congenital DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology EH ethnology ET etiology [decs.bvs.br]

Tests for common etiologic diagnosis of neuropathy were negative. Acute porphyria was one of differential diagnosis. Typical pattern of porphyric neuropathy is predominant motor neuropathy. Sensory predominant is uncommon presentation. [neurology.org]

Conclusion Overall, VP unequivocally appears to be the only possible etiology of this patient’s neurological symptoms, with supporting clinical, biological, and genetic evidence. [frontiersin.org]

Etiology Variegate porphyria is caused by a deficiency in protoporphyrinogen oxidase (PPOX; the penultimate enzyme in the heme biosynthesis pathway) that leads to an accumulation of porphyrins and their precursors in the liver (delta-aminolevulinic acid [orpha.net]

Qualificadores Permitidos Inglês : BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications CN congenital DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology [decs.bvs.br]

Pathophysiology and Epidemiology In people suffering from variegate porphyria porphyrins (protoporphyrin and coproporphyrin) accumulate in the body because of inadequate heme synthesis. [ic.steadyhealth.com]

The word "variegate" was first used in the superb epidemiologic study that Dean and Barnes published in 1959 [2], in which the genetic pedigrees of some 200 individuals with variegate porphyria were traced to their origin in a single pair of married Dutch [muse.jhu.edu]

Epidemiology This type of porphyria is most common in the white population of South Africa; about 3 per 1,000 people in this population are diagnosed each year. The disorder occurs much less frequently in other parts of the world. [wikidoc.org]

[citation needed] Treatment[edit] Liver transplant has been used in the treatment of this condition.[9] Epidemiology[edit] In South Africa, the prevalence of variegate porphyria is approximately 1 in 300.[10] In Finland, the prevalence is approximately [en.wikipedia.org]

Pathophysiology and Epidemiology In people suffering from variegate porphyria porphyrins (protoporphyrin and coproporphyrin) accumulate in the body because of inadequate heme synthesis. [ic.steadyhealth.com]

Porphyrias are classified in two ways, by symptoms and by pathophysiology. Symptomatically, acute porphyrias primarily present with nervous system involvement, often with severe abdominal pain, vomiting, neuropathy and mental disturbances. [indigitrax.org.au]

IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Italy Michela Brena, MD,Post-Graduate School of Dermatology and Venereology, University of Milan, Italy Carlo Gelmetti, MD,chairman of the Pediatric Dermatology Unit, Department of Pathophysiology [routledge.com]

The article provides a brief description of heme biosynthesis and the pathophysiology that underlie an acute attack. [clinicaladvisor.com]

MB One of the recent studies from our center that has greatly helped us understand the pathophysiology of acute intermittent porphyria was conducted on the explanted liver of a patient who had a liver transplant for this disease. [hematologyandoncology.net]

Future attacks can be prevented by avoiding triggering factors. Frequent attacks that are cyclic can be prevented by administration of a GnRH analogue. [porphyriafoundation.org]

1. Stojeba N, Meyer C, Jeanpierre C, et al. Recovery from a variegate porphyria by a liver transplantation. Liver Transpl. 2004;10(7):935-938.
2. Ramanujam V-MS, Anderson KE. Porphyria Diagnostics – Part 1: A brief overview of the porphyrias. Curr Protoc Hum Genet. 2015;86:17.20.1-17.20.26.
3. Christiansen AL, Aagaard L, Krag A, Rasmussen LM, Bygum A. Cutaneous Porphyrias: Causes, Symptoms, Treatments and the Danish Incidence 1989-2013. Acta Derm Venereol. 2016;96(7):868-872
4. Besur S, Hou W, Schmeltzer P, Bonkovsky HL. Clinically Important Features of Porphyrin and Heme Metabolism and the Porphyrias. Fuller M, ed. Metabolites. 2014;4(4):977-1006.
5. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
6. Horner ME, Alikhan A, Tintle S, Tortorelli S, Davis DM, Hand JL. Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Int J Dermatol. 2013;52(12):1464-1480.