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

  After administration of phenobarbital, reddish urine was noted and muscular weakness progressed to atonic quadraparesis. Porphyria attack was diagnosed from high urinary levels of aminolevulinic acid and porphobilinogen. [ncbi.nlm.nih.gov]

  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]

  During an attack, a person may also experience muscle weakness, seizures, and mental changes such as anxiety and hallucinations. [en.wikipedia.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]

• Abdominal Pain

  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]

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

• Vomiting

  Abstract Variegate 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 [ncbi.nlm.nih.gov]

  Acute attacks usually begin in adulthood and cause abdominal pain, vomiting, diarrhoea and constipation. During an attack, a person may also experience muscle weakness, seizures, and mental changes such as anxiety and hallucinations. [en.wikipedia.org]

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

• 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]

  Acute attacks usually begin in adulthood and cause abdominal pain, vomiting, diarrhoea and constipation. During an attack, a person may also experience muscle weakness, seizures, and mental changes such as anxiety and hallucinations. [en.wikipedia.org]

  Patients complain about abdominal pain, vomiting diarrhea and/or constipation. The attack is also characterized by muscle weakness, seizures and mental changes (e.g. anxiety, hallucinations etc). There are different triggers of the attacks. [ic.steadyhealth.com]

• Nausea

  At the age of 45 years, she developed abdominal pain, nausea, vomiting and seizures. After administration of phenobarbital, reddish urine was noted and muscular weakness progressed to atonic quadraparesis. [ncbi.nlm.nih.gov]

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

  Patients also experience nausea, vomiting, constipation, and increased heart rate and blood pressure. These symptoms and signs are all due to the effects of the disease on the nervous system. [sema4genomics.com]

  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]

  […] consists of the following: Manage fluid and electrolyte imbalances Control seizures with benzodiazepines, magnesium sulphate or gabapentin Control severe tachycardia and hypertension with beta blockers Manage severe pain with opioid analgesics Reduce nausea [dermnetnz.org]

• 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]

• Hypertension

  […] 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]

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

  Management of acute attacks consists of the following: Manage fluid and electrolyte imbalances Control seizures with benzodiazepines, magnesium sulphate or gabapentin Control severe tachycardia and hypertension with beta blockers Manage severe pain with [dermnetnz.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]

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

  Management of acute attacks consists of the following: Manage fluid and electrolyte imbalances Control seizures with benzodiazepines, magnesium sulphate or gabapentin Control severe tachycardia and hypertension with beta blockers Manage severe pain with [dermnetnz.org]

• Hand Deformity

  In addition we describe, in one case, two features not previously reported: skin disease in areas unexposed to light and a severe sensory neuropathy which may account at least in part for the hand deformities of this disorder. [ncbi.nlm.nih.gov]

• 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]

  Photosensitive skin Photosensitive skin rashes Photosensitivity Sensitivity to sunlight Skin photosensitivity Sun sensitivity The PPOX gene is responsible for making an enzyme known as protoporphyrinogen oxidase. [rarediseases.info.nih.gov]

• Blister

  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]

  Erythropoietic porphyrias are characterized by increased sensitivity to sunlight that causes chronic blistering ( Figure 1 ) ( Signal, 1993 ). [bcm441.kericolabroy.bergbuilds.domains]

• Cutaneous Manifestation

  Our patient, a 36-year-old woman, has severe cutaneous manifestations. [ncbi.nlm.nih.gov]

  Women using oral contraceptives are particularly susceptible to the cutaneous manifestations of VP. Most individuals (at least 75%) who inherit a PPOX mutation are asymptomatic throughout life. [themedicalbiochemistrypage.org]

  manifestations, notably extreme mechanical fragility of the skin, particularly areas exposed to the sunlight, and by episodes of abdominal pain and neuropathy. [medical-dictionary.thefreedictionary.com]

• Skin Rash

  rashes Photosensitivity Sensitivity to sunlight Skin photosensitivity Sun sensitivity The PPOX gene is responsible for making an enzyme known as protoporphyrinogen oxidase. [rarediseases.info.nih.gov]

  The skin rash is similar to that in porphyria cutanea tarda (see above). Sometimes the only symptom of these mixed porphyrias is the skin rash. [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]

• Hyperpigmentation

  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]

  Facial hyperpigmentation and hypertrichosis may occur. [ncbi.nlm.nih.gov]

  Blisters are slow to heal and can scar leaving patches of skin that are abnormally dark (hyperpigmentation) or light (hypopigmentation). Skin symptoms may be less common in individuals who live in nontropical climates. [rarediseases.org]

• 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]

• Dark Urine

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

  urine Non-acute/cutaneous porphyria is a chronic disease caused by the accumulation of porphyrins in the skin, causing photosensitive skin lesions. [health24.com]

  They include abdominal pain which is severe and poorly localized (most common, 95% of patients experience), Urinary symptoms (Dysuria, urinary retention/incontinence or dark urine), peripheral neuropathy (patchy numbness and paresthesias), Proximal motor [house.wikia.com]

  Other useful clues are a history of dark urine, especially reddish urine, tachycardia, and systemic arterial hypertension during attacks. [clinicaladvisor.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]

  Even a purple hue or red urine may be seen. Diagnosis Edit Porphyrin studies Edit Porphyria is diagnosed through biochemical analysis of blood, urine, and stool. [house.wikia.com]

• Seizure

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

  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]

• 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]

  You could also feel agitated, confused, or get seizures. Some complications you could get are: Long-term pain Kidney damage Liver cancer Symptoms of Cutaneous Porphyria Symptoms of cutaneous porphyria happen when your skin is in sunlight. [webmd.com]

• Neurologic Manifestation

  Though variegate prophyria with neurologic manifestations is not uncommon syringomyelic type of sensory loss is most unusual. [ncbi.nlm.nih.gov]

  It is characterized by cutaneous photosensitivity and/or various neurological manifestations. Protoporphyrinogen oxidase catalyses the penultimate step of haem biosynthesis, and mutations in the PPOX gene have been coupled to VP. [doi.org]

  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]

• 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]

• Dysarthria

  A 29-yr-old man with neurological symptoms that included tremor, dysarthria, and loss of consciousness was diagnosed as having variegate porphyria, because of increased urinary excretion of delta-aminolevulinic acid, porphobilinogen, uroporphyrin, and [ncbi.nlm.nih.gov]

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

  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. Copyright 2012 Wiley Periodicals, Inc. [ncbi.nlm.nih.gov]

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

  There may be autonomic instability and electrolyte changes, particularly hyponatremia. Epilepsy and mental disturbances occur commonly. [muse.jhu.edu]

  Indeed, hyponatremia is common enough in acute attacks that its presence may help support suspicion of underlying porphyria. [clinicaladvisor.com]

We describe our experience with treatment with heme arginate, and provide evidence that heme arginate results in a prompt and statistically significant improvement in symptoms. [ncbi.nlm.nih.gov]

With early diagnosis and treatment, variegate porphyria is rarely life threatening and it doesn’t usually get worse with time. [rarediseases.info.nih.gov]

Pauline Harper and Staffan Wahlin, Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria, Current Treatment Options in Gastroenterology, 10.1007/s11938-007-0044-9, 10, 6, (444-455), (2008). Richard S. [dx.doi.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]

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

Very rare childhood cases have been ascribed to the presence of 2 mutant protoporphyrinogen oxidase genes in the same individual. [11, 18] Prognosis Mild attacks of variegate porphyria may resolve within a few to several days with conservative management [emedicine.medscape.com]

Prognosis With early diagnosis and treatment acute attacks are rarely fatal and the disease is rarely progressive. However, variegate porphyria is a risk factor for the development of hepatocellular carcinoma. [orpha.net]

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]

[…] aminolevulinic acid are found during episodic attacks of systemic symptoms. [5, 9] Acute attack symptoms are caused by dysfunctions of central, autonomic, and peripheral nervous systems that appear to be effects of deranged heme synthesis on neurons. [10] Etiology [emedicine.medscape.com]

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]

Four South African children manifesting variegate porphyria were compound heterozygotes with the founder mutation on one allele, but a different mutation apparently encoding an enzyme with enough residual activity to enable survival, on the other. [13] Epidemiology [emedicine.medscape.com]

Summary Epidemiology Prevalence is around 1/100,000 in European countries and much higher in South Africa due to a founding effect. Clinical description Generally the disease manifests after puberty and preferentially affects women. [orpha.net]

Balances summaries of relevant pathophysiology with clear, practical clinical guidance to help you thoroughly understand the underlying science of diseases. [books.google.com]

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]

Pathophysiology Inherited as an autosomal dominant trait, variegate porphyria is biochemically characterized by accumulations of the photosensitizing porphyrins protoporphyrin and coproporphyrin. [5] In addition, abnormally high levels of the porphyrin [emedicine.medscape.com]

Recognition of the carrier status is the first step of an efficient preventive care. This could be achieved by measurement of PO activity which is a sensitive and specific but tedious method. [ncbi.nlm.nih.gov]

Desnick, RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice, Proceedings of the National Academy of Sciences, 111, 21, (7777), (2014). Jennifer A. Tracy and P. [dx.doi.org]

Symptoms - Variegate porphyria Causes - Variegate porphyria Prevention - Variegate porphyria Not supplied. [checkorphan.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.