The clinical presentation is quite similar across all types of acute hepatic porphyrias. The "acute attacks" are the hallmark of these disorders, most frequently encountered after puberty in women [5]. Most important symptoms are related to the gastrointestinal tract and include intense and nonspecific abdominal pain that may be cramping, constipation, nausea, vomiting, decreased bowel sounds and diarrhea in some patients [1] [3] [5]. Head, neck and chest pain are seen in approximately 50% of cases, as are hypertension, tachycardia, mental changes (restlessness, anxiety, insomnia, disorientation, paranoia and hallucinations) and convulsions [1] [9]. Muscle weakness, tremor, diaphoresis, dysuria, dark urine, bladder distension and severe neuropathy may be encountered as well [5], and a missed diagnosis may lead to severe and irreversible motor neuropathy [2]. In addition to acute attacks, some forms may be accompanied by cutaneous symptoms, such as HCP, in which photosensitivity and blistering skin lesions (vesicles, bullae and erosions with scarring) are constitutive features [1] [5].

• Pain

  paralysis, fatigue, respiratory paralysis Autonomic2,4,10 nausea and vomiting, hypertension, tachycardia, constipation, severe diffuse abdominal pain, diarrhea, pain in back or chest Cutaneous symptoms1,5 lesions on sun-exposed skin occur only in hereditary [porphyria.ca]

  The pain of acute attacks can be severe, requiring hospitalisation for pain management and a lead-up to other possible causes of pain. Severe electrolyte imbalance, respiratory distress, or seizures should prompt admission to intensive care. [dermnetnz.org]

  Clinical features Some common signs and symptoms of porphyria are as follows: Acute colicky abdominal pain in the left lower abdomen which lasts for hours to days. The pain is rarely accompanied by fever, leukocytosis, or peritonitis. [lecturio.com]

  Rapid heart rate High blood pressure 4 Cutaneous (Skin) Symptoms* Leisons or blisters on sun-exposed skin 5 Gastrointestinal Constipation or diarrhea 6 Autonomic Nervous System Unexplained abdominal pain Pain in back or chest Nausea and vomiting Other [porphyria.com]

  When these are found in patients with diverse symptoms, including abdominal pain, joint pain, muscle pain, fibromyalgia, anxiety and chronic fatigue syndrome, such patients, unfortunately, are labeled as having porphyria when they do not. [aasldpubs.onlinelibrary.wiley.com]

• Weakness

  Severe, Diffuse Abdominal Pain1-5 + 1 Or More Of The Following PERIPHERAL Nervous System Limb weakness or pain CENTRAL Nervous System Anxiety Confusion AUTONOMIC Nervous System Nausea Vomiting CUTANEOUS† Skin lesions on sun- exposed areas *There are 4 [porphyria.ca]

  She received heme and supportive therapy with resolution of weakness and seizures but had a spontaneous abortion. Discussion We present 3 patients with AIP with varying degrees and patterns of motor weakness. [karger.com]

  Weakness or paralysis. AHP can affect the nerves that control your muscles. You may get weakness in your legs, belly, and arms. Without treatment, you may lose the ability to move. Continued Mood changes. [webmd.com]

  Nerves that control muscles can be affected, leading to weakness, usually beginning in the shoulders and arms. The weakness can progress to virtually all the muscles, including those involved in breathing. Tremors and seizures may develop. [merckmanuals.com]

  AHPs are associated with potentially life-threatening acute attacks characterised by a range of debilitating symptoms including severe, diffuse abdominal pain, nausea, weakness and constipation. [medthority.com]

• Anemia

  During childhood and adulthood a mild residual anemia is chronically observed. In our case the girl suffering from abdominal and cerebral pain, only one we find skin alteration, without any apparent clinical or ematological sign of anemia. [clinicsinsurgery.com]

  However, in this study, the patient had normocytic and normochromic type of anemia. [scielo.br]

  Four new chapters cover anemias unique to the newborn period, pathology of LHC and other histiocytic disorders, tumors of the spleen, and pathology and classification of myeloproliferative disorders and mast cell disease. [books.google.com]

  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]

  Symptoms associated with hepatic disease include: limb pain neuropathy hypertension tachycardia (fast heartbeat) electrolyte imbalance Symptoms associated with erythropoietic disease include: extreme skin sensitivity to light anemia (when the body does [healthline.com]

• Fatigue

  CHRONIC AHP SYMPTOMS Chronic symptoms, such as anxiety, nausea, pain, and fatigue can take a serious toll on some people with AHP. [porphyria.com]

  Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP;Average Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants [kofam.ch]

  Secondary endpoints included ALA and porphobilinogen levels, hemin use, and scores for pain, fatigue, and nausea. [ashclinicalnews.org]

  RESULTS: All patients identified prodromal symptoms that began days prior to acute severe pain; the most common included confusion ("brain fog"), irritability, and fatigue. [ncbi.nlm.nih.gov]

  Common symptoms of AHP include severe, diffuse abdominal pain, weakness, nausea, and fatigue. Long term symptoms and complication can include chronic neuropathic pain, hypertension, chronic kidney disease and liver disease. [trialsitenews.com]

• Fever

  In the case of acute abdominal pain with fever, the suspicion of appendicitis is obvious. An appendectomy scar is thus often found amongst porphyria patients. [lecturio.com]

  VP), hereditary coproporphyria (HCP), and the extremely rare ALA dehydratase-deficiency porphyria (ADP).1,6,7 †Cutaneous symptoms occur only in HCP and VP.5 AHP Features a combination of Symptoms In addition to severe, diffuse abdominal pain without fever [porphyria.ca]

  AIP is the most common form of hepatic porphyria and symptoms are often begin after puberty and consist of acute neurovisceral signs, abdominal pain, vomiting, constipation, tachycardia, fever, hypertension and alterations in the central nervous system [medcraveonline.com]

  She did not present vomit or alteration of alvo or fever. Neurological examination was normal. [clinicsinsurgery.com]

• Dyspnea

  Some patients have prolonged symptoms of lesser intensity (eg, obstipation, fatigue, headache, back or thigh pain, paresthesia, tachycardia, dyspnea, insomnia, depression, anxiety or other disturbances of mood, seizures). [msdmanuals.com]

• Abdominal Pain

  Clinical description All acute hepatic porphyrias can be accompanied by neuro-visceral attacks that appear as intense abdominal pain (in 85-95% of cases) over one to two weeks, neurological symptoms (muscular weakness, sensory loss or convulsions) and [orpha.net]

  Abdominal pain. A surgeon observed the patient for abdominal pain, and Ranitidine was administrated. We were limited in using drugs for the hypertensive crisis. [content.sciendo.com]

  From Wikidata Jump to navigation Jump to search porphyria that has symptom abdominal pain, has symptom neuropathy, has symptom autonomic instability and has symptom psychosis acute hepatic porphyria porphyria, acute hepatic porphyria edit English acute [wikidata.org]

  AHP can be diagnosed using a PBG urine test, and testing should be considered in all patients presenting with recurrent abdominal pain of unknown origin. [medthority.com]

  […] progress to respiratory failure in hours or days Bladder paresis Agitation, confusion, combativeness, seizure Differential Diagnosis Diffuse Abdominal pain Abdominal aortic aneurysm Aortocaval fistula Acute gastroenteritis Aortoenteric fisulta Appendicitis [wikem.org]

• Vomiting

  Additional treatments include painkillers and antiemetics (to treat nausea and vomiting), chemically-induced menopause with hormonal suppression therapy, and liver transplantation. [ema.europa.eu]

  Severe, Diffuse Abdominal Pain1-5 + 1 Or More Of The Following PERIPHERAL Nervous System Limb weakness or pain CENTRAL Nervous System Anxiety Confusion AUTONOMIC Nervous System Nausea Vomiting CUTANEOUS† Skin lesions on sun- exposed areas *There are 4 [porphyria.ca]

  Gastrointestinal disorders Irritable bowel syndrome (IBS) Acute gastroenteritis with vomiting Hepatitis Crohn's disease Neurological/neuropsychiatric disorders Fibromyalgia Guillain-Barré syndrome Psychosis Gynecological disorders Endometriosis Abdominal [mygi.health]

  Gastrointestinal disorders Irritable bowel syndrome (IBS) Acute gastroenteritis with vomiting Hepatitis Crohn’s disease Neurological/neuropsychiatric disorders Fibromyalgia Guillain-Barré syndrome Psychosis Gynecological disorders Endometriosis Abdominal [porphyria.com]

  As a result, substances for making haem accumulate in the body (particularly in the liver) and become toxic, causing attacks of severe abdominal pain, vomiting and nervous system disorders, such as seizures (fits), depression and anxiety. [io.nihr.ac.uk]

• Nausea

  Severe, Diffuse Abdominal Pain1-5 + 1 Or More Of The Following PERIPHERAL Nervous System Limb weakness or pain CENTRAL Nervous System Anxiety Confusion AUTONOMIC Nervous System Nausea Vomiting CUTANEOUS† Skin lesions on sun- exposed areas *There are 4 [porphyria.ca]

  The most common adverse events were nausea (27% on givosiran compared to 11% on placebo), and reactions at the injection site (16.7% on the drug and 0% on placebo). [biospace.com]

  CHRONIC AHP SYMPTOMS Chronic symptoms, such as anxiety, nausea, pain, and fatigue can take a serious toll on some people with AHP. Signs and Symptoms of AHP The symptoms of AHP can vary from person to person and change over time. [mygi.health]

  CHRONIC AHP SYMPTOMS Chronic symptoms, such as anxiety, nausea, pain, and fatigue can take a serious toll on some people with AHP. [porphyria.com]

  AHP is life-threatening due to the possibility of paralysis and respiratory arrest during attacks and debilitating in the long term because of symptoms such as pain, nausea, seizures and skin blistering. [io.nihr.ac.uk]

• Constipation

  AHPs are associated with potentially life-threatening acute attacks characterised by a range of debilitating symptoms including severe, diffuse abdominal pain, nausea, weakness and constipation. [medthority.com]

  Most important symptoms are related to the gastrointestinal tract and include intense and nonspecific abdominal pain that may be cramping, constipation, nausea, vomiting, decreased bowel sounds and diarrhea in some patients. [symptoma.com]

  […] or without neurovisceral symptoms VP Autosomal dominant inheritance Symptoms include acute-onset abdominal pain with nausea, vomiting, constipation, and tachycardia (identical to those of AIP) Skin symptoms are common and can present with or without [arupconsult.com]

  Nervous System Limb weakness or pain Numbness Fatigue Tiredness Paralysis Respiratory paralysis Sensory loss 3 Cardiovascular Rapid heart rate High blood pressure 4 Cutaneous (Skin) Symptoms* Leisons or blisters on sun-exposed skin 5 Gastrointestinal Constipation [porphyria.com]

  Symptoms include pain in the chest or abdomen, vomiting, and diarrhea or constipation. During an attack, symptoms can include muscle numbness, tingling, paralysis, cramping, and personality or mental changes. [icd9data.com]

• Severe Abdominal Pain

  As a result, substances for making haem accumulate in the body (particularly in the liver) and become toxic, causing attacks of severe abdominal pain, vomiting and nervous system disorders, such as seizures (fits), depression and anxiety. [io.nihr.ac.uk]

  abdominal pain Neurological symptoms that occurred around the time of severe abdominal pain (i.e. muscle weakness, sensory loss, confusion, hallucinations, seizures) Gastrointestinal manifestations that occurred around the time of severe abdominal pain [invitae.com]

  This can cause attacks of severe abdominal pain, vomiting and nervous system disorders, such as seizures, depression and anxiety. AHP is life-threatening due to the possibility of paralysis and respiratory arrest during attacks. [ema.europa.eu]

  Depending on the specific type, AHP patients can suffer from a range of symptoms including acute and/or recurrent life-threatening attacks with severe abdominal pain, peripheral and autonomic neuropathy, neuropsychiatric manifestations, cutaneous lesions [clinicaladvisor.com]

  The second most common form, acute intermittent porphyria (AIP), is characterized by life-threatening attacks of severe abdominal pain, constipation, tachycardia, and neuropsychiatric abnormalities. [amboss.com]

• Jaundice

  Renal tubular disorders and renal stone disease 168 Clinical biochemistry of nutrition 180 Nutritional disorders and their management 200 Clinical biochemistry of the gastrointestinal tract 214 Assessment of hepatic function and investigation of jaundice [books.google.com]

  壊血病 scorbutus 核黄疸 Kernikterus (独), kernicterus, nuclear jaundice 家族性アミロイドーシス familial amyloidosis 家族性アミロイドポリニューロパチー familial amyloidotic polyneuropathy 家族性LCAT欠損症 familial lecithin cholesterol acyltransferase deficiency 家族性高コレステロール血症 familial hypercholesterolemia [jsge.or.jp]

  M. was born after a natural childbirth with a weighed of 2.810 gr; she manifested light asphyxia and jaundice at birth, for this reason she were recovered in UTIN, where she was in observation for three days. [clinicsinsurgery.com]

  […] disease-causing mutation will express symptoms. [2] Individuals who are homozygous for a specific mutation (K404E) or compound heterozygous with a null allele in CPOX have a more severe erythropoietic porphyria, harderoporphyria, [5] characterized by neonatal jaundice [ippn.info]

  A 27-year-old man was admitted to our hospital for evaluation and treatment of liver dysfunction with jaundice and hepatosplenomegaly. The patient had severe photosensitivity from childhood. [ci.nii.ac.jp]

• Hypertension

  Patients usually present with abdominal pain, impaired intestinal motility, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine. [ncbi.nlm.nih.gov]

  After the admission, the patient had the hypertensive crisis. Hypertension is common in patients with AIP, but the hypertensive crisis is rare. [content.sciendo.com]

  Content is provided from medical therapies to surgery on the patient with portal hypertension. [books.google.com]

  Head, neck and chest pain are seen in approximately 50% of cases, as are hypertension, tachycardia, mental changes (restlessness, anxiety, insomnia, disorientation, paranoia and hallucinations) and convulsions. [symptoma.com]

  […] lead to a diagnosis1,2: Central2,4 anxiety, depression, confusion, seizures, hallucinations, insomnia Peripheral2,4 muscle weakness, neuropathic pain in limbs, sensory loss, paralysis, fatigue, respiratory paralysis Autonomic2,4,10 nausea and vomiting, hypertension [porphyria.ca]

• Tachycardia

  Patients usually present with abdominal pain, impaired intestinal motility, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine. [ncbi.nlm.nih.gov]

  Tachycardia and hyponatremia are often present in acute attacks of AHP.1,2,7 These symptoms reflect neurotoxic effects across the autonomic, peripheral, and central nervous systems. [porphyria.ca]

  and no fever Skin is never affected HCP Autosomal dominant inheritance Symptoms include acute-onset abdominal pain with nausea, vomiting, constipation, and tachycardia (identical to those of AIP) Skin symptoms are rare but can present with or without [arupconsult.com]

  Tachycardia and hypertension can be treated with a β-blocker, but this should be done cautiously if there is evidence of hypovolemia. [cghjournal.org]

  Head, neck and chest pain are seen in approximately 50% of cases, as are hypertension, tachycardia, mental changes (restlessness, anxiety, insomnia, disorientation, paranoia and hallucinations) and convulsions. [symptoma.com]

• Chest Pain

  pain in the head and neck and/or chest. [symptoma.com]

  Generally, the most common symptoms being abdominal pain (74%), back pain (56%), chest pain (58%), and nausea and vomiting (73%) 8,10, however, there can be a wide range of neuropsychiatric and cutaneous manifestations as well. [radiopaedia.org]

  The symptoms can include: Belly pain, often severe Chest pain Faster heart rate and higher blood pressure Limb and back pain Muscle weakness Tingling and loss of sensation Cramping Vomiting and constipation You may notice changes in your personality or [webmd.com]

  Symptoms of an attack include abdominal pain, chest pain, vomiting, confusion, constipation, fever, high blood pressure, and high heart rate. The attacks usually last for days to weeks. [clinicsinsurgery.com]

  Visceral manifestations (i) Abdominal pain (ii) Other locations of pain (chest, back, and limb) More than 30 presentations over the past couple of years for abdominal pain and some for chest pain; has necessitated at least 6 computerized tomography (CT [hindawi.com]

• Muscle Weakness

  Motor involvement during acute attacks may lead to persistent muscle weakness and muscle atrophy between attacks. [msdmanuals.com]

  Muscle weakness, tremor, diaphoresis, dysuria, dark urine, bladder distension and severe neuropathy may be encountered as well, and a missed diagnosis may lead to severe and irreversible motor neuropathy. [symptoma.com]

  Nerve damage and associated muscle weakness from a severe attack improves over time, but such improvement may take many months to resolve fully. [porphyriafoundation.org]

  Acute porphyria can also affect the nervous system causing numbness and muscle weakness. This can even occur in the chest wall, which can in turn lead to breathing difficulties. [recordatirarediseases.com]

  Acute Hepatic Porphyria Symptoms Can Impact Quality of Life Affected individuals can experience some combination of the following symptoms: Severe, diffuse abdominal pain, vomiting/nausea, dark/reddish urine Muscle weakness, numbness, respiratory failure [alnylam.com]

• Back Pain

  Generally, the most common symptoms being abdominal pain (74%), back pain (56%), chest pain (58%), and nausea and vomiting (73%) 8,10, however, there can be a wide range of neuropsychiatric and cutaneous manifestations as well. [radiopaedia.org]

  Symptoms may include vomiting, abdominal or back pain, weakness in arms or legs, and mental symptoms. Laboratory tests are done on urine samples taken during the attack. [merckmanuals.com]

  The symptoms can include: Belly pain, often severe Chest pain Faster heart rate and higher blood pressure Limb and back pain Muscle weakness Tingling and loss of sensation Cramping Vomiting and constipation You may notice changes in your personality or [webmd.com]

  The motor, sensory, and autonomic nervous systems are often affected, resulting in autonomic changes (e.g., tachycardia, hypertension), muscle weakness; sensory loss; and pain in the back, chest, and extremities. [ncbi.nlm.nih.gov]

• Myalgia

  Four patients were assessed as having AEs possibly related to study drug, including injection site reaction (mild and self-limiting), hypersensitivity, myalgia, headache, moderate renal impairment (in a patient with a history of moderate renal impairment [dddmag.com]

  Possibly or definitely related AEs reported in two or more cases were injection site reactions and myalgia; all of these events were mild. [businesswire.com]

• Neck Pain

  Her medical history includes hypertension, generalized seizures, cardiac arrythmia, and chronic neck pain. She had been hospitalized previously with episodes of abdominal pain and generalized seizures. [karger.com]

• Photosensitivity

  Indications for Testing Diagnostic testing for porphyrias should be performed in individuals who present with severe, diffuse neuropathic abdominal pain and accompanying symptoms and in individuals with cutaneous photosensitivity. [arupconsult.com]

  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]

  Differential diagnoses for variagate porphyria and hereditary coproporphyria also include photosensitivity. [orpha.net]

  They present similarly except that HCP and VP are also associated with cutaneous photosensitivity. [epilepsy.com]

  Porphyria cutanea tarda (PCT) is the most common form and presents with chronic, blistering cutaneous photosensitivity and tea-colored urine. [amboss.com]

• Blister

  For individuals with blistering or non-blistering skin lesions, total plasma porphyrins or erythrocyte porphyrins should be tested. [invitae.com]

  Urine Porphyrin Fractionation and Quantitation Urine porphyrin fractionation and quantitation is the initial test used to evaluate patients for porphyrias that manifest with blistering cutaneous photosensitivity. [arupconsult.com]

  AHP is life-threatening due to the possibility of paralysis and respiratory arrest during attacks and debilitating in the long term because of symptoms such as pain, nausea, seizures and skin blistering. [io.nihr.ac.uk]

  The cutaneous porphyrias are rare inherited metabolic disorders that present with blistering of the skin, pain, and/or redness and swelling in sun-exposed areas. [alnylam.com]

  The skin is extremely light-sensitive and responds to exposure with blistering and delayed healing. Scars on the face and at the back of the hands can often be found. [lecturio.com]

• Cutaneous Manifestation

  This panel may be appropriate for individuals with signs and symptoms of an acute hepatic porphyria with or without cutaneous manifestations. [invitae.com]

  Generally, the most common symptoms being abdominal pain (74%), back pain (56%), chest pain (58%), and nausea and vomiting (73%) 8,10, however, there can be a wide range of neuropsychiatric and cutaneous manifestations as well. [radiopaedia.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]

• Hypertrichosis

  […] erythropoietic porphyria (CEP) a form of erythropoietic porphyria, with cutaneous photosensitivity leading to mutilating lesions, hemolytic anemia, splenomegaly, excessive urinary excretion of uroporphyrin and coproporphyrin, and invariably erythrodontia and hypertrichosis [medical-dictionary.thefreedictionary.com]

  HIV Estrogen therapy Sunlight exposure Pathophysiology Clinical findings Cutaneous manifestations Increased fragility of sun-exposed skin → blistering and impaired healing ( blistering photosensitivity ) Healing results in scarring and milia formation Hypertrichosis [amboss.com]

  Similarly, patients show increased hair growth (hypertrichosis) and hyperpigmentation. The skin manifestation of the PCT can be presumed without a prophylaxis disfiguring extent. [lecturio.com]

  Other common symptoms may include thickening of the skin, hypo- and hyperpigmentation, hypertrichosis, cutaneous scarring, and deformities of the fingers, eyelids, lips, nose, and ears. [mayomedicallaboratories.com]

• Hyperpigmentation

  Secondary infections can cause areas of hypo- or hyperpigmentation or sclerodermatous changes and may result in the development of alopecia at sites of repeated skin damage. [mayomedicallaboratories.com]

  […] therapy Sunlight exposure Pathophysiology Clinical findings Cutaneous manifestations Increased fragility of sun-exposed skin → blistering and impaired healing ( blistering photosensitivity ) Healing results in scarring and milia formation Hypertrichosis Hyperpigmentation [amboss.com]

  Similarly, patients show increased hair growth (hypertrichosis) and hyperpigmentation. The skin manifestation of the PCT can be presumed without a prophylaxis disfiguring extent. [lecturio.com]

  Fragile, poorly healing skin with pruritus, hyperpigmentation and hypertrichosis are other features. Forehead, cheeks, ears and backs of hands are most commonly affected but all skin exposed to the sun can be affected. [patient.info]

• Psychiatric Manifestation

  Motor     Motor paresis   Central nervous system    Impairment of bulbar or respiratory function (respiratory paralysis)    Convulsions/seizures   Psychiatric    Psychiatric manifestations (behavior change, agitation, anxiety, and depression) Has ongoing [hindawi.com]

  Managing Chronic Problems The suicide rate in patients with acute porphyria is increased significantly compared with the rate in the general population, possibly owing to depression caused by ongoing psychiatric manifestations or because of chronic pain [cghjournal.org]

  Clinical conditions involve autonomic neuropathy, peripheral neuropathy and brain dysfunction, progressing generally in the following order: first, severe abdominal pain; second, psychiatric manifestations and finally neurological disorders (Blom 1996 [scielo.br]

  Psychiatric symptoms may occur both during acute episodes or become chronic diagnoses in the form of depression, anxiety, hallucinations, psychosis, or delirium.14 Endocrine Manifestations Hyponatremia is a common manifestation of AIP. [dovepress.com]

  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 [cancertherapyadvisor.com]

• Delusion

  Sleep disturbance, anxiety, delirium, hallucinations, depressed mood, and paranoid delusions may be present.81,82 Lethargy and coma occur rarely. Peripheral motor neuropathies may lead to foot or wrist drops. [epilepsy.com]

  Other psychiatric symptoms such as anxiety, restlessness, insomnia, depression, mania, hallucinations, delusions, confusion, catatonia, and psychosis may occur. [33] Underlying liver disease [ edit ] Some liver diseases may cause porphyria even in the [en.wikipedia.org]

  Rarely these are more severe with psychosis, delusions and hallucinations. Mental changes resolve completely on remission. [onlinelibrary.wiley.com]

• Mood Swings

  He suffered from mood swings, abdominal pain and occasional paranoia. He was initially diagnosed with stress. Acute intermittent porphyria (AIP) is a rare sub-type that can be passed on by receiving one copy of the faulty gene from a single parent. [house.fandom.com]

  He suffered from mood swings, abdominal pain and occasional paranoia. He was initially diagnosed with stress. [house.wikia.com]

• Urinary Retention

  The most typical clinical signs include nausea, vomiting, constipation, diarrhea, urinary retention, tachycardia, hypertension, mental symptoms, and muscle pain and weakness. [revistanefrologia.com]

  Other symptoms may include (7): nausea vomiting constipation pain in the back, arms and legs muscle weakness (due to the effects on nerves supplying the muscles) urinary retention palpitation (due to a rapid heart rate and often accompanied by an increased [content.sciendo.com]

  Neuropathy may progress rapidly to give complete paralysis, incontinence or urinary retention, swallowing difficulties and respiratory failure. [journals.sagepub.com]

  Bladder dysfunction can present with urinary retention, urinary incontinence, or dysuria.9 Renal Manifestations Porphyria related nephropathy is due to genetic variations in renal transporters. [dovepress.com]

• Dark Urine

  You could also have: Dark urine Sensitive skin Belly pain Nausea Seizures An attack usually starts with severe stomach pain and can last for days. You'll usually need to go to the hospital for treatment. [webmd.com]

  Signs and Symptoms Diagnosis Treatment Symptoms vary depending on the type of porphyria, but some of the more common include: Dark urine Skin sensitivity, including blistering, of areas exposed to the light, such as the face and back of hands Pain in [ucsfhealth.org]

  Muscle weakness, tremor, diaphoresis, dysuria, dark urine, bladder distension and severe neuropathy may be encountered as well, and a missed diagnosis may lead to severe and irreversible motor neuropathy. [symptoma.com]

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

• Dysuria

  Bladder dysfunction (urinary retention, incontinence, and dysuria) Endorsed dysuria on some admissions. HTN Noted in our patient. Chronic kidney disease Present, necessitating dialysis. [hindawi.com]

  Muscle weakness, tremor, diaphoresis, dysuria, dark urine, bladder distension and severe neuropathy may be encountered as well, and a missed diagnosis may lead to severe and irreversible motor neuropathy. [symptoma.com]

  Bladder dysfunction can present with urinary retention, urinary incontinence, or dysuria.9 Renal Manifestations Porphyria related nephropathy is due to genetic variations in renal transporters. [dovepress.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.fandom.com]

• Red Urine

  Urine tests are irrelevant to the diagnosis of EPP, except to exclude other types of porphyria, because protoporphyrins are not excreted in urine. [arupconsult.com]

  Red urine that fluoresces in nappies can allow an easy bedside diagnosis. [ 3 ] There is severe photosensitivity. Pruritus and erythema followed by vesicle and bullous formation occur on exposure to sunlight. [patient.info]

  In acute intermittent porphyria, for example, urine may be red to brown urine and may darken when exposed to air, light, and warmth. [50] The urine of patients with porphyria cutanea tarda is red to brown in natural light (red-wine urine) and pink to [emedicine.medscape.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.fandom.com]

• Bladder Distention

  Additional common manifestations include nausea; vomiting; tachycardia; hypertension; mental symptoms; extremity, neck, or chest pain; headache; muscle weakness; sensory loss; tremors; sweating; dysuria; and bladder distention. [ashpublications.org]

• Seizure

  We studied one patient with major motor seizures and acute intermittent porphyria. The seizure disorder was exacerbated by phenytoin and did not respond to a high-carbohydrate diet or to intravenous hematin. [ncbi.nlm.nih.gov]

  AHP is life-threatening due to the possibility of paralysis and respiratory arrest during attacks and debilitating in the long term because of symptoms such as pain, nausea, seizures and skin blistering. [io.nihr.ac.uk]

  […] autosomal dominant, are associated with seizures:78 acute intermittent porphyria (AIP) hereditary coproporphyria (HCP) variegate porphyria (VP) HCP and VP are much less common than AIP. [epilepsy.com]

• Confusion

  Severe, Diffuse Abdominal Pain1-5 + 1 Or More Of The Following PERIPHERAL Nervous System Limb weakness or pain CENTRAL Nervous System Anxiety Confusion AUTONOMIC Nervous System Nausea Vomiting CUTANEOUS† Skin lesions on sun- exposed areas *There are 4 [porphyria.ca]

  […] attacks that appear as intense abdominal pain (in 85-95% of cases) over one to two weeks, neurological symptoms (muscular weakness, sensory loss or convulsions) and psychological symptoms (irritability, anxiety, auditory or visual hallucinations, mental confusion [orpha.net]

  RESULTS: All patients identified prodromal symptoms that began days prior to acute severe pain; the most common included confusion ("brain fog"), irritability, and fatigue. [ncbi.nlm.nih.gov]

  Signs and Symptoms of AHP 1 Central Nervous System Confusion Anxiety Seizures Insomnia Hallucinations Depression 2 Peripheral Nervous System Limb weakness or pain Numbness Fatigue Tiredness Paralysis Respiratory paralysis Sensory loss 3 Cardiovascular [porphyria.com]

• Agitation

  You may get irritated, agitated, or feel like you need to move around. It’s also common to worry a lot or feel depressed and lose interest in activities or get confused. You could also see things that aren’t there or get really paranoid. [webmd.com]

  […] diarrhea Port wine-colored urine Diffuse musculoskeletal pain Neurologic symptoms Headache Sensory loss (40%) An indication of a severe and potentially life-threatening attack Neuropathy can progress to respiratory failure in hours or days Bladder paresis Agitation [wikem.org]

  Central nervous system symptoms include agitation, confusion, and depression. Convulsions occur in 10%–20% of patients. [cghjournal.org]

  […] anxiety/depression along with some agitation episodes.   [hindawi.com]

  Mental symptoms, such as irritability, restlessness, insomnia, agitation, tiredness, and depression, are common. Nervous system symptoms are numerous. [merckmanuals.com]

• Peripheral Neuropathy

  Features of Textbook of Peripheral Neuropathy Include : ̈ Practical yet comprehensiveóan accessible ìgo-toî reference for clinicians ̈ Covers all clinically relevant peripheral neuropathies ̈ Clinical Pearls and Key Points are set off from the text for [books.google.com]

  AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. [uniprot.org]

  Porphyric neuropathy. in: Dyck P.J. Thomas P.K. Griffin J.W. Low P.A. Poduslo J.F. Peripheral neuropathy. 3rd edition. Saunders, Philadelphia1992: 1161-1168 Bonkovsky H.L. Barnard G.F. [liver.theclinics.com]

  It has also been reported that severe porphyric neuropathy can occur in isolation without other preceding symptoms [4] and that peripheral neuropathy occurs in up to 40% of patients during an acute attack of porphyria [3, 6, 7]. [karger.com]

  Peripheral neuropathy may cause pain in the extremities, back, and chest, with muscle weakness that usually begins proximally in the upper extremities. [cghjournal.org]

• Insomnia

  Mental symptoms, such as irritability, restlessness, insomnia, agitation, tiredness, and depression, are common. Nervous system symptoms are numerous. [merckmanuals.com]

  Signs and Symptoms of AHP 1 Central Nervous System Confusion Anxiety Seizures Insomnia Hallucinations Depression 2 Peripheral Nervous System Limb weakness or pain Numbness Fatigue Tiredness Paralysis Respiratory paralysis Sensory loss 3 Cardiovascular [porphyria.com]

  Insomnia. That means you’ll have trouble falling or staying asleep. Low levels of electrolytes. Low sodium levels, or hyponatremia, can be an early sign of AHP. You could also get low levels of magnesium in your blood. [webmd.com]

  Attacks of acute porphyria may unfold or progress with the following symptoms: anxiety, restlessness and insomnia severe abdominal pain pain in your arms, legs or back vomiting and constipation high blood pressure (hypertension) muscle pain, tingling, [britishlivertrust.org.uk]

To make the diagnosis of acute hepatic porphyrias, a thorough patient history that will reveal presence of any of the mentioned porphyrias (having in mind the autosomal dominant pattern of inheritance), recent use of drugs or habits that may have precipitated the attacks, as well as history of similar symptoms, is essential. Together with a thorough physical examination, sufficient information can be gathered to suspect porphyria as an underlying cause. To confirm the diagnosis, urine and fecal testing for heme precursors and toxic metabolites should be performed. A distinction between subtypes can be made based on the obtained findings. AIP is suspected when markedly higher levels (20-100x higher) of ALA, PBG and uroporphyrin are found in urine, whereas detection of high coproporphyrin III levels in urine and stool, in addition to ALA and PBG in urine, is highly specific for HCP [5]. VP, on the other hand, is distinguished from HCP by confirming the presence of protoporphyrin in stool [5]. Urine and stool samples should be obtain during or right after the acute attacks [2]. A definite diagnosis is made through genetic tests, specifically polymerase chain reaction (PCR), which will detect the exact type of mutation [1].

• Hyponatremia

  Seizures may occur in 20% of cases, particularly in patients with hyponatremia. [revistanefrologia.com]

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

  Tachycardia and hyponatremia are often present in acute attacks of AHP.1,2,7 These symptoms reflect neurotoxic effects across the autonomic, peripheral, and central nervous systems. [porphyria.ca]

  Hyponatremia Hyponatremia is a relatively common metabolic manifestation accompanying acute attack. It is usually mild and easily corrected. [signavitae.com]

• Protoporphyrin Increased

  […] fecal isocoproporphyrin is a sufficient but not necessary indicator of PCT/HEP, increased metal-free and zinc-bound protoporphyrin in erythrocytes is only found in HEP. [gastrojournal.org]

• Coproporphyrin Increased

  During acute attacks, VP is characterized by increased fecal protoporphyrin and coproporphyrin. In addition, there are increased levels of urinary ALA, PBG, and coproporphyrin III. [cancertherapyadvisor.com]

Initial therapeutic measures of acute hepatic porphyrias are focused on symptom alleviation - management of tachycardia, electrolyte dysbalance (hyponatremia is common, and often the cause of seizures) and gastrointestinal irritation [8]. Phenytoin or valproic acid should be avoided in management of seizures, as they may cause more severe symptoms [2]. Instead, benzodiazepines, gabapentin, magnesium and propofol (in the setting of refractory seizures) are used. Intravenous administration of hemin (a synthetic form of heme), however, is the mainstay of treatment, especially when dealing with acute attacks [2] [10]. Hemin is able to expand the pool of heme in hepatocytes, which produces a negative feedback mechanism that will reduce the production of heme precursors, most notably ALA [2]. Intravenous infusions will lead to resolution of symptoms within 3-4 days, and the lipophilic form (hematin), or heme arginate, is given in doses of 3 mg/kg per 24 hours as a single dose for 4 days [9]. For more severe enzyme deficiencies that cause recurrent life-threatening attacks and predispose patients to progressive motor neuropathies, liver transplantation may be indicated, but proper follow-up and rigorous anticoagulant therapy is mandatory, since a very high risk for hepatic artery thrombosis has been noted [9].

Before the introduction of modern critical care and directed therapy, mortality rates exceeded 35%, but with early identification and increased awareness of the disorder, patients achieve a good prognosis through long-term monitoring and avoidance of factors that are known to induce acute attacks [2]. However, numerous complications may arise, especially if the diagnosis is made late, most important being irreversible nerve degeneration (characteristic for AIP), renal insufficiency, chronic hypertension and hepatocellular carcinoma, which seems to be age-related and more commonly encountered among patients suffering from ongoing liver disease [2] [6].

Acute hepatic porphyrias are all caused by genetic deficiencies of enzymes involved in one of the steps of heme synthesis, many of which occur in the liver. Although only 15% of total heme is synthesized in the liver, genetic mutations reduce enzymatic activity by 50% in AIP, HCP and VP, whereas 95% reduction is seen in ADP [5]. Apart from an autosomal recessive pattern of inheritance seen in ADP, all hepatic porphyrias are caused by autosomal dominant mutations, leading to accumulation of neurotoxic substances in the liver, presumably γ-aminobutyric acid analogs and/or porphobilinogen (PBG) [5].

Prevalence rates of acute hepatic porphyrias significantly vary across different types and geographical regions. Overall prevalence rate of AIP in Europe is estimated at 1 in 75,000 individuals, ranging from 1 in 1,000 in northern Sweden to 2 in 100,000 in Finland, while Argentina reports rates of 1 in 125,000 individuals [1]. On the other hand, valegriate porphyria (VP) is most commonly encountered in South Africa, where 1 in 300 individuals suffer from this type of porphyria due to founder effect [6]. Other countries report much lower rates (2 per 100,000 in Finland and 1 per 600,000 in Argentina) [1]. Up to 2015, only 6 cases of ADP are reported [6]. Numerous precipitating factors or events are well-established inducers of acute attacks: lipophilic drugs (rifampicin, sulfonamide antibiotics, barbiturates and hydantoins) [6], corticosteroids, androgens, alcohol, organic solvents, pesticides, but also profound emotional stress, caloric deprivation that leads to severe fasting and physical effort [1] [6]. It must be noted that some types of hepatic porphyria, such as AIP, are more prevalent among women [6].

Heme formation is a complex metabolic pathway involving eight different enzymes, all being potential targets for genetic mutations and the occurrence of porphyrias [7]. 85% of heme is formed in erythrocytes, and only 15% in the liver, but about 80% of heme synthesized in this organ is necessary for activity of cytochromal P450 enzymes and the electron transport chain in the TCA cycle, which are essential for degradation of toxic chemical and energy formation, respectively [1]. In the setting of genetic mutations that cause deficiencies of enzymes involved in heme synthesis, the pathogenesis of porphyrias stems from insufficient heme production and consequent hepatic accumulation of its precursors, in the attempt to accelerate the production of heme. As enzyme deficiencies impair the ability of the liver to produce heme, these precursors accumulate and become toxic (presumably γ-aminobutyric acid analogs, ALA, and/or porphobilinogen) and their deleterious effects develop through interaction with γ-aminobutyric acid (GABA) or glutamate receptors, the sites where main neuronal transmitters exert their effects [2] [5]. For symptoms to appear, however, the accumulation of these metabolites is not sufficient, but intake of certain drugs, stress, or severe caloric deprivation causes further saturation of cytochromal enzymes and even larger accumulation of toxic metabolites, eventually breaching the threshold of tolerance by the body resulting in the onset of symptoms.

Genetic counselling may be highly recommended for families with a positive history for porphyrias. For those in whom the diagnosis is confirmed, several preventive measures may be of significant benefit [2] [8]:

• Avoiding use of hazardous drugs and exposure to substances that are known inducers of acute attacks.
• Avoid periods of starvation and profound fasting.
• Prophylactic therapy with hematin.
• Regular screening - Abdominal ultrasonography and serum alpha-fetoprotein levels performed on an annual basis after 50 years of age is recommended, primarily to identify early signs of liver disease and hepatocellular carcinoma.

Porphyrias are a group of genetic disorders that arise as a result of deficiency of enzymes involved in the formation of heme, a vital constituent of hemoglobin and cytochromal enzymes that participate in metabolism of numerous drugs in the liver and in the tricyclic acid cycle (TCA), where they are necessary cofactors in the electron transport chain [1]. Based on the onset of symptoms, porphyrias are generally divided into acute and non-acute, and a further classification according to the type of symptoms (neurovisceral and/or cutaneous) can be made as well [1] [2]. Additionally, porphyrias can be classified into hepatic and erythropoietic, depending the site of overproduction of toxic metabolites [3], and four hepatic porphyrias are recognized in literature [4] [5] [6]:

• δ-aminolevulinic acid dehydratase deficiency (ADP) porphyria - Only a six cases of ADP have been described in literature up to today, in which the second step of heme synthesis (condensation of two molecules of δ-aminolevulinic acid - ALA into porphobilinogen) is affected by autosomal recessive mutations [2].
• Acute intermittent porphyria (AIP) - Considered as one of the most common forms of porphyria, AIP is inherited through autosomal dominant patterns, and is caused by mutations in hydroxymethylbilane synthase (HMB-synthase) gene, responsible for the third step of heme synthesis - conversion of porphobilinogen (PBG) into uroporphyrinogen [2]. The clinical presentation appears in only 10% of mutation carriers and comprises typical acute attack consisting of nonspecific abdominal pain, nausea, tachycardia, vomiting, constipation, mental changes, convulsions, hypertension and pain in the head, neck and/or thorax [1].
• Hereditary coproporphyria (HCP) - Deficiency of coproporphyrinogen oxidase (CPOX), necessary for the sixth step of heme formation - conversion of coproporphyrinogen III to protoporphyrinogen IX, through autosomal dominant mutations of the CPOX gene is the mechanism of disease in this type of porphyria [1]. The majority of patients exhibit acute attacks, while 20% can also present with skin-related symptoms, such as photosensitivity and blistering skin lesions [1].
• Variegate porphyria (VP) - Like AIP and HCP, variegate porphyria (VP) is inherited by autosomal dominant transfer of mutated genes that code for protoporphyrinogen oxidase (PPOX), which is necessary for the conversion of protoporphyrinogen to protoporphyrin, the seventh and second-last step in heme synthesis [6]. Adult-onset of cutaneous blistering lesions (subepidermal vesicles, erosions, bullae) of the sun-exposed skin and acute attacks of abdominal and chest pain, constipation, muscle weakness that can be severe enough to cause paralysis of the limbs and respiratory muscles, as well as psychiatric disturbances are main symptoms of VP [7].

Two main features are shared by all porphyrias. Firstly, the onset of symptoms stems from accumulation of toxic substances of the heme pathway due to enzyme deficiencies; and secondly, these metabolites are not sufficient by themselves to cause symptoms [4]. Acute attacks are precipitated by various factors and events, including alcohol, pesticides, organic solvents, caloric deficiency, corticosteroids, and numerous lipophilic drugs (barbiturates, rifampicin, sulfonamide antimicrobials etc.) [1] [6]. For this reason, the diagnosis of hepatic porphyrias can be made by detecting heme precursor metabolites in urine or feces after use of certain drugs, substances or nutritional-related effects. Treatment principles comprise discontinuation of potentially hazardous drugs, administration of hematin (a synthetic form of heme that inhibits production of toxic metabolites), dextrose, symptomatic care, and in most severe cases, liver transplantation [8].

Porphyrias are a group of inherited disorders that cause insufficient formation of heme, a precursor of hemoglobin and a vital constituent of various liver enzymes involved in metabolism of numerous drugs and toxic substances. Based on their clinical features and site of occurrence, they can be divided into acute or non-acute, hepatic or erythropoietic (originating from the liver or red blood cells, respectively) and neurovisceral or cutaneous, implying that symptoms may be related either to the nervous system and internal organs or the skin. Acute hepatic porphyrias are a group of disorders in which enzyme deficiencies cause insufficient formation of heme in the liver and subsequent accumulation of toxic metabolites of this pathway in the same organ. Delta-aminolevulinic acid dehydratase deficiency (ADP) porphyria, acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP) are representatives of this group. For symptoms to appear, enzyme deficiencies are not sufficient by themselves, but additional factors are necessary to trigger their onset. Examples are use of drugs metabolized by enzymes that use heme as its substrate, such as rifampicin, barbiturates, and sulfonamide antibiotics, whereas corticosteroids and androgens, profound fasting due to starvation, emotional stress, exposure to organic solvents, pesticides, and alcohol are other notable examples. The hallmark of hepatic porphyrias are "acute attacks" of nonspecific and intense abdominal pain accompanied by nausea, vomiting, cramping, constipation and deceased bowel sounds, hence the term acute hepatic porphyria. Additional signs include head, neck and chest pain, hypertension, seizures, mental changes (restlessness, anxiety, confusion, insomnia, disorientation), and neuropathies that can induce severe muscle weakness. The diagnosis can be made by detecting toxic metabolites in urine or feces and genetic testing may be performed as a confirmation. Treatment initially focuses on alleviation of symptoms through stabilizing blood pressure and seizures, as well as gastrointestinal complaints. The mainstay of therapy, however, is administration of synthetic heme (known as hematin or heme arginate), which increases the pool of heme in the liver, thus reducing the production of toxic metabolites. Because acute attacks may be recurrent and severe, and even life-threatening, liver transplantation may be considered. For the same reason, a late diagnosis is detrimental, as current therapeutic modalities and preventive strategies (avoiding use of drugs or other factors that can precipitate the onset of symptoms) can successfully treat the condition and prevent long-term sequelae.

1. Szlendak U, Bykowska K, Lipniacka A. Clinical, Biochemical and Molecular Characteristics of the Main Types of Porphyria. Adv Clin Exp Med. 2016;25(2):361-368.
2. Bissell DM, Wang B. Acute Hepatic Porphyria. J Clin Transl Hepatol. 2015;3(1):17-26.
3. Karim Z, Lyoumi S, Nicolas G, Deybach JC, Gouya L, Puy H. Porphyrias: A 2015 update. Clin Res Hepatol Gastroenterol. 2015;39(4):412-425.
4. Siegesmund M, van Tuyll van Serooskerken AM, Poblete-Gutiérrez P, Frank J. The acute hepatic porphyrias: current status and future challenges. Best Pract Res Clin Gastroenterol. 2010;24(5):593-605.
5. Balwani M, Desnick RJ. The porphyrias: advances in diagnosis and treatment. Blood. 2012;120(23):4496-4504. .
6. 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.
7. Singal AK, Anderson KE. Variegate Porphyria. 2013 Feb 14. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
8. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
9. Singal AK, Parker C, Bowden C, Thapar M, Liu L, McGuire BM. Liver Transplantation in the Management of Porphyria. Hepatology (Baltimore, Md). 2014;60(3):1082-1089
10. Pischik E, Kauppinen R. An update of clinical management of acute intermittent porphyria. Appl Clin Genet. 2015;8:201-214.