Presentation
Motor paresis or poor respiratory effort may be present. [ncbi.nlm.nih.gov]
The clinical presentations of porphyric neuropathy range from mild focal neuropathy to more severe presentations with a Guillain-Barré-like picture [ 3, 6, 11 ]. Here, we report 3 cases of porphyria with differing neurological presentations. [karger.com]
Acute hepatic porphyrias (AHPs) can present as episodes of acute porphyria with abdominal pain, autonomic dysfunction (hypertension, tachycardia, and gastrointestinal disorders), and deep motor neuropathy. [revespcardiol.org]
In this issue of the SAMJ, an atypical neurological presentation of AIP in a young man is described. [16] Two points are of particular interest. [scielo.org.za]
There are eight different porphyrias, which can be grouped into those presenting with acute attacks (acute porphyrias) and those presenting with light-sensitive skin problems (skin porphyrias), although there is some overlap. [pulsetoday.co.uk]
Entire Body System
- Weight Loss
If weight loss is desired, it is advisable to contact a physician and dietitian. Premenstrual attacks often resolve quickly with the onset of menstruation. [porphyriafoundation.org]
The most common identified triggers for acute attacks are medications, weight loss diets, and surgery. [19] Many medications have been associated with AIP including antibiotics, hormonal contraceptives, seizure medications, anesthetics, and HIV treatment [en.wikipedia.org]
First acute attacks have been reported following weight loss surgery. 18 Some women suffer monthly recurrent attacks during the luteal phase of their menstrual cycles and can have symptomatic improvement with a gonadotropin‐releasing hormone analogue [aasldpubs.onlinelibrary.wiley.com]
If weight loss is desired, it is advisable to contact a physician and dietician. Premenstrual attacks often resolve quickly with the onset of menstruation. [rarediseases.org]
- Surgical Procedure
A surgical procedure. Sometimes, infection somewhere in the body. There are certain medicines that you should avoid if you have this type of porphyria. Recommended lists of medicines to avoid are available. [patient.info]
Gastrointestinal
- Abdominal Pain
A 34-year-old pregnant woman who presented for evaluation of severe, persistent abdominal pain demonstrates the often elusive nature of this condition. A 34-year-old pregnant woman presented for evaluation of severe, persistent abdominal pain. [mdedge.com]
Case Report A 21-year-old woman presented to us with the complaints of abdominal pain and vomiting. Her abdominal pain and nausea started 15 days ago and gradually increased. She used paracetamol 500 mg twice a day. [mjdrdypu.org]
At age 2, case 9 experienced an episode of mild abdominal pain after the molecular diagnosis of AIP, so he was admitted to the hospital and diagnosed with pain of unknown origin (urine PBG was not measured to assess for a possible attack). [analesdepediatria.org]
During the examination, only the diffuse abdominal pain without accompanying signs of peritonism was relevant. [revespcardiol.org]
The following clinical features may be present during an attack: Severe, poorly localised abdominal pain. Pain in back and legs. Nausea, vomiting and constipation. [pulsetoday.co.uk]
- Acute Abdomen
abdomen and Guillain-Barre syndrome. [scielo.br]
We rule out acute abdomen. We want to highlight the importance of including AIP in the differential diagnosis of acute abdomen. [mjdrdypu.org]
We describe a patient with VP who received class Ic antiarrhythmic agents for paroxysmal atrial fibrillation (AF) and presented with an acute episode of porphyria, which consisted of acute abdomen and syndrome of inappropriate antidiuretic hormone secretion [revespcardiol.org]
Table 3 Presentation of acute crisis: symptoms and signs Symptoms and signs (in order of incidence) Features May be misdiagnosed as Abdominal pain Recurrent, severe, poorly localized Another cause of acute abdomen Associated nausea and vomiting Endometriosis [academic.oup.com]
Acute abdomen from surgical or gynecological causes as well as acute viral gastroenteritis are other common differentials, but with acute porphyria, there is no rebound tenderness. [ncbi.nlm.nih.gov]
Cardiovascular
- Tachycardia
[…] and tachycardia as found in our case. [mjdrdypu.org]
However, these acute attacks are variable and can include vomiting, diarrhea, constipation, urinary retention, acute episodes of neuropathic symptoms, psychiatric symptoms, seizures, respiratory paralysis, tachycardia, and hypertension. [mayocliniclabs.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]
Tachycardia and hyponatremia are common during attacks. In cases with cardiac arrhythmia and respiratory paralysis (rare), attacks can be fatal. [orpha.net]
Acute porphyria should be excluded in any case of unexplained severe abdominal pain, especially if associated with tachycardia and neurological symptoms. [academic.oup.com]
- Palpitations
[…] vomiting Muscle pain, tingling, numbness, weakness or paralysis Red or brown urine Mental changes, such as anxiety, confusion, hallucinations, disorientation or paranoia Breathing problems Urination problems Rapid or irregular heartbeats you can feel (palpitations [mayoclinic.org]
Acute attacks, typically consist of severe abdominal pain, nausea, constipation, palpitations, sweating, confusion, and other neurological manifestations such as peripheral neuropathy, seizures, and paresis, tachycardia and hypertension. [1] [2] [5]. [ncbi.nlm.nih.gov]
Other symptoms may include: vomiting constipation pain in the back, arms and legs muscle weakness (due to effects on nerves supplying the muscles) urinary retention palpitations (due to a rapid heart rate and often accompanied by increased blood pressure [porphyriafoundation.org]
93 Blisters 96 Burning/stinging pain 96 Fatigue 72 Fragile skin 86 Red/swollen skin 86 Dark/reddish urine 64 Dark/reddish urine 55 Sores/crusting 50 Muscular pain 63 Abnormal hair growth 33 Blisters 32 Muscular weakness 59 Increased pigmentation 30 Palpitations [tidsskriftet.no]
Common Symptoms and Signs of AHPs in Subjects With Clinically Active Disease Symptoms Signs Pain Systemic arterial hypertension (43%) Abdominal (74%) Chronic kidney disease (29%) Back (56%) Palpitations/tachycardia (19%) Chest (58%) Hyponatremia (20%) [aasldpubs.onlinelibrary.wiley.com]
Musculoskeletal
- Muscle Weakness
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]
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]
weakness) (Medical Research Council) [oatext.com]
Typically, patients tend to be young healthy females presenting with several days of non-specific neurovisceral symptoms including abdominal pain, nausea, vomiting, extremity pain, muscle weakness, altered mental affect, and even seizures in 20% of cases [first10em.com]
- Back Pain
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. [msdmanuals.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]
but can be associated with back pain or pain in the limbs. [academic.oup.com]
Protoporphyric liver disease may cause severe abdominal pain, especially in the right upper quadrant, and back pain. [bloodjournal.org]
Skin
- Sweating
Other common symptoms include Rapid heart rate Elevated blood pressure Sweating Restlessness Difficulty sleeping Most of these symptoms, including the digestive ones, result from effects on the nervous system. [msdmanuals.com]
[…] pain abdomen (85-95%), vomiting (50%), constipation (50%), peripheral neuropathy (42-68%), seizures (10-16%), delirium, coma and depression. [4] Autonomic disturbances may manifest as urinary retention, paralytic ileus, restlessness, tremor, excessive sweating [joacp.org]
Acute attacks, typically consist of severe abdominal pain, nausea, constipation, palpitations, sweating, confusion, and other neurological manifestations such as peripheral neuropathy, seizures, and paresis, tachycardia and hypertension. [1] [2] [5]. [ncbi.nlm.nih.gov]
It is proposed to be secondary to excessive loss due to vomiting, diarrhoea, sweating or increased renal loss due to osmotic diuresis after glucose infusion and iatrogenic fluid substitute without electrolyte replacement. [signavitae.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]
Over time, in CEP, HEP and PCT scarring, pigment changes, infection, and excessive hair growth (hypertrichosis) can occur. [aasldpubs.onlinelibrary.wiley.com]
Skin thickening, focal hypopigmentation and hyperpigmentation, and hypertrichosis of the face and extremities are characteristic. Secondary infection and bone resorption may lead to disfigurement of the face and hands. [bloodjournal.org]
[…] autonomic instability (hypertension, tachycardia, abdominal pain, nausea, vomiting, and constipation), dehydration and electrolyte imbalance (hyponatremia, hypokalemia, and hypocalcemia), and dermatologic features (photosensitivity, skin fragility, hypertrichosis [ajp.psychiatryonline.org]
- Hirsutism
Severe scarring is rare, as are pigment changes, friability, and hirsutism. Hemolysis and anemia are usually absent or mild. [bloodjournal.org]
Urogenital
- Hematuria
Two critical laboratory clues are red urine—which often is mistaken for a UTI or hematuria—and hyponatremia. 1 Another porphyria hallmark is triggers. These include drugs, carbohydrate deprivation, smoking, and stress. [mdedge.com]
Neurologic
- Agitation
The patient was treated with beta-blockers and a carbohydrate-rich diet; her alterations of consciousness, disorientation, and agitation resolved, leaving no sequelae. [elsevier.es]
Agitation, insomnia, rarely psychosis Contrary to popular belief, long-term mental health problems are no more frequent in porphyria than in other chronic illnesses, and there is no evidence that King George III suffered from any kind of porphyria! [pulsetoday.co.uk]
Agitation, confusion, combativeness and other acute neuropsychiatric features are common and sometimes progress to coma. Convulsions may result from porphyria itself or from hyponatremia. [porphyriafoundation.org]
Mental symptoms, such as irritability, restlessness, insomnia, agitation, tiredness, and depression, are common. Nervous system symptoms are numerous. [msdmanuals.com]
Acute porphyria can also cause mental health (psychiatric) problems including agitation, mania, depression and hallucinations. Symptoms are described more fully later. [patient.info]
- Insomnia
Mental symptoms, such as irritability, restlessness, insomnia, agitation, tiredness, and depression, are common. Nervous system symptoms are numerous. [msdmanuals.com]
[…] features Fever GI symptoms : severe abdominal pain, nausea, vomiting Neurological abnormalities Polyneuropathy : non-specific pain, weakness/fatigue, paresthesia, paresis Seizures Psychiatric abnormalities ; : hallucinations, disorientation, anxiety, insomnia [amboss.com]
Agitation, insomnia, rarely psychosis Contrary to popular belief, long-term mental health problems are no more frequent in porphyria than in other chronic illnesses, and there is no evidence that King George III suffered from any kind of porphyria! [pulsetoday.co.uk]
Usual signs and symptoms of acute porphyria A prodrome consisting of minor behavioral changes usually precedes an acute episode and includes anxiety, restlessness, or insomnia. [cancertherapyadvisor.com]
- Paresis
Neurological manifestations can affect the central nervous system as much as the peripheral nervous system (myalgia, paresis, ascending flaccid paralysis of the limbs, or convulsions) and can lead to severe complications such as motor paralysis. [orpha.net]
Porphyria should be considered as a differential diagnosis in acute abdomen cases of unknown origin and associated with neurological disorders such as paresis, hydroelectrolytic and psychiatric disorders, especially in patients with triggering factors [scielo.br]
Acute crises may vary from a single attack that aborts quickly to those that go on to have frequent life-threatening attacks with multisystem involvement, respiratory, and bulbar paresis. [academic.oup.com]
Motor paresis or poor respiratory effort may be present. [ncbi.nlm.nih.gov]
[…] accumulation of porphobilinogen ( PBG ) and δ-aminolevulinic acid ( ALA ) → symptoms Clinical features Fever GI symptoms : severe abdominal pain, nausea, vomiting Neurological abnormalities Polyneuropathy : non-specific pain, weakness/fatigue, paresthesia, paresis [amboss.com]
- Neurologic Manifestation
Neurological manifestations of acute intermittent porphyria. Cell Mol Biol (Noisy-le-grand) 2009;55(1):72-83. [ Links ] 3. Simon NG, Herkes GK. The neurologic manifestations of the acute porphyrias. [scielo.org.za]
Neurological manifestations are probably due to the neurotoxic effects of porphyrin precursors, ALA being the most significant. [tandfonline.com]
These attacks manifest as intense abdominal pain (>95% of cases) and neurological and/or psychological symptoms. The abdominal pain is often associated with lumbago irradiating to the thighs, and with nausea, vomiting and relentless constipation. [orpha.net]
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]
[Crossref] Solinas C, Vajda FJ (2008) Neurological complications of porphyria. J Clin Neurosci 15: 263-268. [Crossref] Pischik E, Kauppinen R (2009) Neurological manifestations of acute intermittent porphyria. [oatext.com]
- Tremor
Tremors and seizures may develop. Other common symptoms include Rapid heart rate Elevated blood pressure Sweating Restlessness Difficulty sleeping Most of these symptoms, including the digestive ones, result from effects on the nervous system. [msdmanuals.com]
[…] symptoms such as pain abdomen (85-95%), vomiting (50%), constipation (50%), peripheral neuropathy (42-68%), seizures (10-16%), delirium, coma and depression. [4] Autonomic disturbances may manifest as urinary retention, paralytic ileus, restlessness, tremor [joacp.org]
Autonomic disturbances may manifest as urinary retention, paralytic ileus, restlessness, tremors, excessive sweating, tachycardia and fluctuating blood pressure, typically labile hypertension. [6] Autonomic dysfunction may be resulting in hypertension [mjdrdypu.org]
Symptoms include abdominal pain, cramps, nausea, tachycardia, muscle pain and weakness, tremors, hyponatremia, hypertension, and excess sweating. [invitae.com]
Workup
The laboratory workup showed normal kidney function, GOT, 41 U/L; GPT, 43 U/L; alkaline phosphatase, 50 IU/L; GGT, 50 IU/L; LDH, 539 IU/L; sodium, 111 mEq/L; and plasma osmolarity, 231 mOsm/L. [revespcardiol.org]
Workup and Diagnosis Most routine investigations may offer information but are not helpful in making a diagnosis, including a diagnosis of porphyria (1). [ajp.psychiatryonline.org]
Urinary porphyrins should have been sent as part of the initial workup and interpreted along with other second-line tests. [cancertherapyadvisor.com]
"Think porphyria" in patients with abdominal pain that is unexplained after an initial workup has excluded common causes such as appendicitis, cholecystitis, pancreatitis, etc. [porphyriafoundation.org]
Serum
- Hyponatremia
The hyponatremia and elevation of creatine kinase was gradually corrected [Table 1]. [mjdrdypu.org]
Hyponatremia may reflect inappropriate antidiuretic hormone secretion. Gastrointestinal or renal sodium loss may contribute. [porphyriafoundation.org]
Hyponatremia Hyponatremia is a relatively common metabolic manifestation accompanying acute attack. It is usually mild and easily corrected. [signavitae.com]
Our patient presented repeatedly with hyponatremia. Marked hyponatremia frequently complicates acute porphyrias (4, 5, 7, 31, 34, 45). [ajp.psychiatryonline.org]
It should be considered in a patient with recurrent abdominal symptoms, intractable hyponatremia, along with neurological manifestations. Early diagnosis can prevent recurrent episodes and can be potentially lifesaving. [tandfonline.com]
Treatment
Supportive and Symptomatic Treatment: Harmful drugs should be stopped immediately and avoided during treatment. For example, metoclopramide should not be given. [porphyriafoundation.org]
[…] prompt treatment of complications. [journals.sagepub.com]
Removal of precipitating factors, treatment of underlying infection, a carbohydrate diet and intravenous (i.v) heme remains mainstay of treatment of an acute attack. [joacp.org]
If the analysis of PBG in 24-h urine cannot be available or will result later, the clinician should start hematin treatment for AIP. AIP is a medical emergency and delay in treatment may contribute to serious or even fatal outcomes. [mjdrdypu.org]
Prognosis
What is the prognosis? Several decades ago the mortality rate for AIP attacks was upwards of 25%. [first10em.com]
It is hoped that this will stimulate more interest in the subject, in order that the diagnosis may be made early and treatment instituted promptly with the expectation of improving the prognosis. [annals.org]
Prognosis Several decades ago the prognosis for acute porphyria with neurological complications was poor, with a reported mortality of 35%. The prognosis remains guarded for those that present with acute porphyria. [ncbi.nlm.nih.gov]
Prognosis In certain patients attacks recur, resulting in the need for repeated and more frequent injections of human hemin. Crippling attacks can possibly indicate the need for a hepatic transplant. [orpha.net]
The prognosis of AIP is usually good if the disorder is recognized before severe nerve damage has occurred and if treatment and preventive measures are begun. [porphyriafoundation.org]
Etiology
Therapy Avoid susceptibility factors and excessive sunlight Phlebotomy Hydroxychloroquine or chloroquine References: [1] [2] [3] Acute intermittent porphyria (AIP) Epidemiology Second most common porphyria Peak incidence : ∼ 30 years Sex: ♀ > ♂ (2:1) Etiology [amboss.com]
Etiology Acute intermittent porphyria is caused by a deficiency of porphobilinogen deaminase (PBG-D; the third enzyme in the heme biosynthesis pathway) that leads to an accumulation of the precursors of porphyrins in the liver (delta-aminolevulinic acid [orpha.net]
Etiology Acute porphyrias are inherited conditions however environmental, e.g., drugs and physiological factors are crucial for clinical manifestation. Epidemiology The autosomal dominant acute porphyrias affect males and females equally. [ncbi.nlm.nih.gov]
Recently, new insight into the etiology of the acute attacks came from several patients with AIP and VP who had chronic attacks that ceased after liver transplantation. 16, 17 Of note, “domino” transplantation of the “porphyric livers” into recipients [bloodjournal.org]
In the present case, the diagnosis was entertained because of the following: 1) the etiologically obscure neurosis or psychosis after an extensive workup, 2) unexplained peripheral neuropathy, 3) indeterminate neurologic spells, 4) hyponatremia of unknown [ajp.psychiatryonline.org]
Epidemiology
[…] uroporphyrin ( tea-colored urine ) Blood tests: ↑ porphyrins, possibly abnormal LFTs Therapy Avoid susceptibility factors and excessive sunlight Phlebotomy Hydroxychloroquine or chloroquine References: [1] [2] [3] Acute intermittent porphyria (AIP) Epidemiology [amboss.com]
Acute intermittent porphyria is the most common form of porphyria. (4-8) EPIDEMIOLOGY Acute intermittent porphyria has a prevalence of 1-2 cases per 100 thousand inhabitants. [scielo.br]
Epidemiology The autosomal dominant acute porphyrias affect males and females equally. [ncbi.nlm.nih.gov]
Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria. Am J Hum Genet 1997 ; 60 : 1373 -1383. ↵ Whatley SD, Puy H, Morgan RR, Robreau A-M, Roberts AG, Nordmann Y, et al. [clinchem.aaccjnls.org]
The epidemiology of hepatocellular carcinoma in patients with Acute Intermittent Porphyria. J Intern Med. 1996; 240:195-201 7) Andant C, Puy H, Faivre J, Deybach JC. Acute hepatic porphyrias and primary liver cancer [Letter]. [porphyriafoundation.org]
Pathophysiology
Stress (e.g., surgery, infection) Pathophysiology : defective PBG-D → accumulation of porphobilinogen ( PBG ) and δ-aminolevulinic acid ( ALA ) → symptoms Clinical features Fever GI symptoms : severe abdominal pain, nausea, vomiting Neurological abnormalities [amboss.com]
The prevalence of AIP has been estimated to be 5-10 cases per 100,000. [3] Pathophysiology Heme is a 64 kDa tetrameric protein present in hemoglobin, myoglobin, respiratory cytochromes and cytochrome P450 enzymes. [1] The heme biosynthetic pathway involves [ncbi.nlm.nih.gov]
The article provides a brief description of heme biosynthesis and the pathophysiology that underlie an acute attack. [cancertherapyadvisor.com]
In this article, the author discusses the history, clinical features, pathophysiology, classification, and treatment of porphyria. [medlink.com]
In AIP, pathophysiology of hyponatremia is only partly understood and can be associated with the syndrome of inappropriate antidiuretic hormone secretion, also contributed to by gastrointestinal or renal sodium loss [ 13 Straume Z, Skuja V, Proskurina [tandfonline.com]
Prevention
Hormone manipulation may be effective in preventing such attacks and some affected women have been treated with gonadotropin-releasing hormone analogues (GnRH or LHRH treatments such as Lupron) to suppress ovulation and prevent frequent, cyclic attacks [porphyriafoundation.org]
Porphyria prevents your body from creating enough enzymes to control the process, and porphyrin builds up. High levels of porphyrin can cause problems throughout your body, depending on where it builds up. [drugs.com]
"It also has a lasting effect of at least one month, which gives us an effective means of preventing acute attacks in seriously afflicted porphyria patients who have limited treatment options." [sciencedaily.com]