Due to hormonal factors, AIP almost always manifests after puberty, especially in women. AIP attacks typically follow a distinct order of events starting with abdominal pain (>95% of attacks), then psychiatric symptoms (eg. hysteria) and finally peripheral and motor neuropathies. Between attacks patients are symptom free. No skin manifestations are observed in patients with AIP during attacks, but neurovisceral signs and symptoms, including abdominal pain associated with lumbago radiating to the thighs, autonomic neuropathies (causing constipation), vomiting, hypertension and tachycardia, may occur. Epigastric and colicky abdominal pain is severe and often lasts for several days but chronic abdominal pain is unusual. Scattered upper body pain may also occur (back, arm and leg pain). Symptoms may also include urinary retention, palpitations and decreased levels of sodium and chloride in the blood. The central nervous system sings of AIP may include seizures, delirium, cortical blindness, irritability, emotionality, anxiety and coma. Peripheral neuropathies may mimic Guillain-Barré syndrome and include weakness that starts in the lower limbs and rises, although any nerve distribution may be observed. A variety of psychiatric symptoms are observed, including depression in most cases, mental changes (confusion and hallucinations) and seizures. Concurrent neurological or abdominal symptoms can be life-threatening and may progress to paralysis and hyponatremia.

The majority of individuals who inherit the HMBS gene mutation never develop symptoms, however, experts recommend that relatives of AIP patients obtain testing. Individuals who have the trait should be educated on how to avoid attacks. Optimal management should include prevention. AIP attacks are most often triggered by exogenous factors (porphyrinogenic drugs, alcohol, infections, fasting and stress), and/or endogenous factors (hormonal).

• Acute Intermittent Porphyria

  We report a 12 year old male child with acute intermittent porphyria, who presented with encephalopathy and transient blindness of cerebral origin. [ncbi.nlm.nih.gov]

  Clinical Defects Acute intermittent porphyria may be complicated by the acute attack, which may be very severe. (See Acute symptoms in porphyria ). [porphyria-professionals.uct.ac.za]

  Acute intermittent porphyria Mnemonic – Medical Institution Mechanism of Acute intermittent porphyria: Approximately 90% of cases of acute intermittent porphyria are due to a mutation that causes decreased amounts of the enzyme, and to a lesser degree [medical-institution.com]

  Keywords: Acute intermittent porphyria, amino levulinic acid, porphobilinogen How to cite this article: Kaur MD, Hazarika N, Saraswat N, Sood R. Acute intermittent porphyria: Diagnostic dilemma and treatment options. [joacp.org]

• Weakness

  […] encoding PBD Prognosis most patients fully recover < 5% have recurrence Presentation Symptoms often nonspecific and vague primary symptoms (5 P’s) severe abdominal p ain without tenderness on palpation neurological symptoms p olyneuropathy seizures, weakness [medbullets.com]

  Thus, AIP should be considered in the differential diagnosis of children presenting with unexplained abdominal pain, seizures, weakness and neuropathy. [ncbi.nlm.nih.gov]

  The weakness usually starts in the lower limbs and ascends, but neuropathies can be observed in any nerve distribution. Patients may develop autonomic neuropathies, such as hypertension and tachycardia. [medical-institution.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]

• Fever

  A biliary colic will present with a colicky RUQ pain yet without fever, leucocytosis, or jaundice. Cholecystitis will present with RUQ pain and fever yet jaundice will be absent. [teachmesurgery.com]

  The term hepatic fever was used for the first time by Charcot in his report published in 1887. Intermittent fever accompanied by chills, right upper quadrant abdominal pain, and jaundice have been established as Charcot's triad. [patient.info]

  […] one acute attack during their lives. acute intermittent porphyria Hematology An AD condition caused by a deficiency of porphobilinogen deaminase, resulting in overproduction of δ-aminolevulinic acid Clinical Recurrent abdominal colic, constipation, fever [medical-dictionary.thefreedictionary.com]

  Jean-Martin Charcot first described acute cholangitis as ‘hepatic fever’. [news-medical.net]

  The classical presentation is the Charcot triad of fever, right upper quadrant abdominal pain, and jaundice, which is only seen in ~40% of patients. [radiopaedia.org]

• Anemia

  Disorders of normal heme synthesis may cause human diseases, including certain anemias (X-linked sideroblastic anemias) and porphyrias. [doi.org]

  A Chinese female patient with very typical AIP symptoms of severe abdominal pain, seizures, hypertension, and tachycardia, accompanied with hyponatremia, anemia, and hyperbilirubinemia. [ncbi.nlm.nih.gov]

  However, lead poisoning causes a decrease in the number of blood cells (anemia), which is not seen in acute intermittent porphyria. [thinkgenetic.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]

• Dutch

  […] cholangeitis, cholangitis (diagnosis), Cholangitis NOS (disorder), Biliary tract infection, Cholangitis (disorder), bile duct; inflammation, inflammation; bile duct, Cholangitis, NOS Portuguese COLANGITE, Colangite NE, Inflamação de canal biliar, Colangite Dutch [fpnotebook.com]

  The HMBS mutations in the Dutch (R167W/R173Q), 7 English (R167W/R167Q), 8 and Spanish (R167W/R167W) patients occurred in exon 10 at CpG dinucleotides, known as mutational hotspots, and altered highly conserved arginines in the enzyme’s active site, which [doi.org]

  NVKC 10 (1985) 223–231 (in Dutch) Google Scholar Beukeveld, G. J. J., Wolthers, B. G., Saene van, J. J. M., Haan de, Th. H. IJ., Ruyter-Buitenhuis, de L. W. and Saene van, R. H. F. [link.springer.com]

  "Dutch government seeks to allow creation of human embryos for research". BioNews. Retrieved 2016-06-10. ^ Reich DA, Lander ES (2001). "On the allelic spectrum of human disease". Trends Genet. 17 (9): 502–510. doi:10.1016/s0168-9525(01)02410-6. [en.wikipedia.org]

  UK, is now estimated at 7 per million. 15 The prevalence in South Africa is much higher at approximately 1200 per million of the European immigrant population, 20 owing to a founder effect resulting from the introduction of the R59W mutation into the Dutch [jcp.bmj.com]

• Abdominal Pain

  The abdominal pain is severe and lasts for several days. Severe abdomen pain of short ( < 1 d) duration or chronic abdominal pain is unusual. [medical-institution.com]

  We reported an adult male patient diagnosed as AIP by finding a mutation in the HMBS gene after recurrent abdominal pain for 10 years. [doi.org]

  An 18-year-old girl was admitted to our hospital with recurrent abdominal pain and 2 episodes of convulsions. She had undergone an appendectomy earlier at another hospital for abdominal pain. [ncbi.nlm.nih.gov]

  Clinical manifestations include photosensitivity, abdominal pain and neuropsychiatric symptoms. [usmle.biochemistryformedics.com]

• Vomiting

  The neurovisceral symptoms consist of autonomic neuropathies (eg, constipation, colicky abdominal pain, vomiting, hypertension), peripheral neuropathy, seizures, delirium, coma, and depression. [medical-institution.com]

  In September 2013, he had abdominal pain, nausea, vomit, and the serum potassium was normal, sodium was 119.7 mmol/L, chloride was 87.3 mmol/L. [doi.org]

  Gradually she also developed diarrhea, vomiting and progressive weakness of her lower limbs and finally flaccid quadriparesis. [joacp.org]

  […] primary symptoms (5 P’s) severe abdominal p ain without tenderness on palpation neurological symptoms p olyneuropathy seizures, weakness, and paralysis p sychiatric symptoms anxiety and insomnia p ort wine-colored urine p recipitated by an exposure vomiting [medbullets.com]

  The abdominal pain is often associated with lumbago irradiating to the thighs, and with nausea, vomiting and relentless constipation. [orpha.net]

• Constipation

  The neurovisceral symptoms consist of autonomic neuropathies (eg, constipation, colicky abdominal pain, vomiting, hypertension), peripheral neuropathy, seizures, delirium, coma, and depression. [medical-institution.com]

  Neurologic symptoms may also develop, including flaccid paralysis, seizures, neuropsychiatric and urinary symptoms such as retention or incontinence and constipation. [doi.org]

  […] symptoms (5 P’s) severe abdominal p ain without tenderness on palpation neurological symptoms p olyneuropathy seizures, weakness, and paralysis p sychiatric symptoms anxiety and insomnia p ort wine-colored urine p recipitated by an exposure vomiting constipation [medbullets.com]

  We report here a 60-year-old non-alcoholic male who had typical manifestations of AIP, including abdominal pain, constipation, tachycardia, hypertension, mental disturbances, psychiatric manifestations, seizures, peripheral neuropathy, and excessive excretion [ncbi.nlm.nih.gov]

• Nausea

  In September 2013, he had abdominal pain, nausea, vomit, and the serum potassium was normal, sodium was 119.7 mmol/L, chloride was 87.3 mmol/L. [doi.org]

  Frequently, nausea and vomiting are present. Patients can have a wide variety of psychiatric symptoms. Usually, patients have concurrent neurologic or abdominal symptoms. Depression is very common. [medical-institution.com]

  We report a case of 33-year-old male patient who presented with recurrent episodes of severe abdominal pain, nausea, vomiting, constipation and numbness of bilateral lower limb extremities. [ncbi.nlm.nih.gov]

• Diarrhea

  Additional symptoms can be loss of vision, sensitivity to light, aches and pains, acne, vomiting, diarrhea, abdominal pain, constipation, and abnormal fat metabolism. [diagnose-me.com]

  The attacks are often linked to menstrual cycles, highlighting the importance of endogenous steroids, especially progesterone, in pathogenesis.[2] The most common presenting is severe abdominal pain, nausea, vomiting, diarrhea, or constipation. [doi.org]

  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]

  Gradually she also developed diarrhea, vomiting and progressive weakness of her lower limbs and finally flaccid quadriparesis. [joacp.org]

  […] months.[2] Abdominal pain, which is associated with nausea and can be severe, is the most common symptom and usually the first sign of an attack.[1][2] Other symptoms may include [1][2]: • Gastrointestinal issues (e.g., nausea, vomiting, constipation, diarrhea [rarediseases.info.nih.gov]

• Hypertension

  The neurovisceral symptoms consist of autonomic neuropathies (eg, constipation, colicky abdominal pain, vomiting, hypertension), peripheral neuropathy, seizures, delirium, coma, and depression. [medical-institution.com]

  Previous reports have focused on hypertension as the principal etiological factor. [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]

• Tachycardia

  […] p ain without tenderness on palpation neurological symptoms p olyneuropathy seizures, weakness, and paralysis p sychiatric symptoms anxiety and insomnia p ort wine-colored urine p recipitated by an exposure vomiting constipation Physical exam vitals tachycardia [medbullets.com]

  We report here a 60-year-old non-alcoholic male who had typical manifestations of AIP, including abdominal pain, constipation, tachycardia, hypertension, mental disturbances, psychiatric manifestations, seizures, peripheral neuropathy, and excessive excretion [ncbi.nlm.nih.gov]

  Patients may develop autonomic neuropathies, such as hypertension and tachycardia. Patients may have very severe abdominal pain lasting several days. Pain of short duration (minutes) or chronic abdominal pain is not observed in AIP. [medical-institution.com]

• Photosensitivity

  The presence of fluorescent red cells (fluorocytes) in AIP is probably under-recognized since AIP is a hepatic porphyria and not associated with photosensitivity. [ncbi.nlm.nih.gov]

  Clinical manifestations include photosensitivity, abdominal pain and neuropsychiatric symptoms. [usmle.biochemistryformedics.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]

  Permanent residual deficits are not uncommon; residual defects during latent periods include polyneuropathy in both conditions, ataxia and retinitis pigmentosa with night blindness in Refsum disease, [7] and photosensitive dermatitis in porphyrias (rare [emedicine.medscape.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]

  The signs may present from birth and include severe photosensitivity, brown teeth that fluoresce in ultraviolet light due to deposition of type one porphyrins and later hypertrichosis. Hemolytic anemia usually develops. [house.wikia.com]

• Hyperpigmentation

  […] symptoms of chronic cholangitis may include: tiredness and fatigue itchy skin dry eyes dry mouth If you have chronic cholangitis for a long time, you may have: pain in the upper right side night sweats swollen feet and ankles darkening of the skin (hyperpigmentation [healthline.com]

• Increased Sweating

  Increased sweating Profuse sweating Sweating Sweating profusely Sweating, increased [ more ] 0000975 Hypertensive crisis 0100735 Paresthesia Pins and needles feeling Tingling [ more ] 0003401 5%-29% of people have these symptoms Arthralgia Joint pain [rarediseases.info.nih.gov]

• Hirsutism

  Most of the time the facial hairs are fine, so the hirsutism is barely noticeable. Sometimes, however, the hair growth can give the appearance of a werewolf, leading to speculations that the myths may have had a medical basis. [scientificamerican.com]

• Muscle Weakness

  The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. [ncbi.nlm.nih.gov]

  Following withdrawal of diclofenac and metoclopramide and treatment with IV 20% dextrose, a marked improvement occurred with resolution of muscle weakness and hyponatremia. [endocrine-abstracts.org]

  Others may include: nausea vomiting constipation pain in the back, arms and legs muscle weakness (due to effects on nerves supplying the muscles) urinary retention palpitation (due to a rapid heart rate and often accompanied by increased blood pressure [web.archive.org]

• Back Pain

  Patient B was a woman, 36 years of age, who was initially under the care of an orthopedic surgeon for severe back pain and was referred to a consultant physician for investigation of multiple symptoms, including urinary retention, dysuria, back pain, [clinchem.aaccjnls.org]

  Back pain (10/32) was the most frequent AIP pain symptom and sweet craving (10/15) was the most frequent PMS symptom. [ncbi.nlm.nih.gov]

  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]

  Symptoms may include vomiting, abdominal or back pain, weakness in arms or legs, and mental symptoms. The most common symptom is generalized abdominal pain that lasts for several hours to days. [msdmanuals.com]

• Myalgia

  Her abdominal pain and myalgia subsided on the third day of dialysis. Her lower limb muscle power improved and she became ambulant by the fourth day. Urinary retention improved within 4 days. Hematin was imported by then from the United States. [ncbi.nlm.nih.gov]

  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]

  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]

• Hysteria

  Snapshot A 32-year-old woman presents to the psychiatric emergency room for uncooperative behavior and hysteria. She complains of abdominal pain. While being evaluated, she had a generalized tonic-tonic seizure. [medbullets.com]

  […] porphyria In porphyria …of hepatic porphyria: (1) In acute intermittent porphyria, also called porphyria hepatica, affected persons have recurrent attacks of abdominal pain and vomiting, weakness or paralysis of the limbs, and psychic changes resembling hysteria [britannica.com]

  Testimony to this is the following quote written as recently as 1995 61 : Psychiatric manifestations[in porphyria] include hysteria, anxiety, depression, phobias, psychosis, organic disorders, agitation, delirium, and altered consciousness ranging from [jcp.bmj.com]

  AIP attacks typically follow a distinct order of events starting with abdominal pain (>95% of attacks), then psychiatric symptoms (eg. hysteria) and finally peripheral and motor neuropathies. Between attacks patients are symptom free. [symptoma.com]

  […] constipation, diarrhea, abdominal distention, ileus) • Urinary tract issues (e.g., urinary retention, urinary incontinence, or dysuria) • Neurological issues (e.g., muscle weakness in the arms or legs, paralysis) • Psychiatric issues (e.g., insomnia, hysteria [rarediseases.info.nih.gov]

• Visual Hallucination

  Psychological symptoms are variable: irritability, emotionality, depression, considerable anxiety and, more rarely, auditory and visual hallucinations, disorientation, mental confusion. [orpha.net]

  On the following day, he developed altered mentation in the form of fluctuating levels of orientation, agitation, irritability, confusion, and visual hallucination (seeing animals) in the ICU. [doi.org]

• Mood Swings

  Mental and neurological symptoms include irritability, confusion, delirium, psychosis, depression, hallucinations, seizures, altered consciousness, mood swings, and paralysis. [diagnose-me.com]

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

• Abnormal Behavior

  On evaluation, she had hyponatremia, episodic abnormal behavior, generalized muscle pain, hypertension, and sinus tachycardia. In view of the above clinical picture, a clinical diagnosis of acute intermittent porphyria was made. [ncbi.nlm.nih.gov]

• Seizure

  While being evaluated, she had a generalized tonic-tonic seizure. She has no family or personal history of seizures. Her serum studies ruled out any metabolic abnormalities that may cause seizures. [medbullets.com]

  Neurontin : for treatment of seizures. Most classic antiseizure medicines can lead to acute porphyria attacks. [medical-institution.com]

  The authors recommend testing for porphyria in cases of Rasmussen encephalitis and other intractable seizures. [ncbi.nlm.nih.gov]

• Confusion

  Peripheral neuropathy (patchy numbness and paresthesias) Psychological disturbances (anxiety, confusion, psychosis, dementia) Precipitated by drugs (drugs that enhance cytochrome P-450 activity, sulfa drugs, barbiturates, some antipsychotics, alcohol) [stepwards.com]

  The disease is clinically manifested with severe abdominal pain, confusion, and seizures which may be life threatening. [ncbi.nlm.nih.gov]

• Peripheral Neuropathy

  The neurovisceral symptoms consist of autonomic neuropathies (eg, constipation, colicky abdominal pain, vomiting, hypertension), peripheral neuropathy, seizures, delirium, coma, and depression. [medical-institution.com]

  Neurologic exam showed extensive peripheral neuropathy. Urine showed high titers of porphobilinogen. [medbullets.com]

  Any part of the nervous system may be involved, with evidence for autonomic and peripheral neuropathy. [usmle.biochemistryformedics.com]

  Both had a very poor quality of life as a result of years of frequent acute porphyria symptoms, chronic peripheral neuropathy and renal failure requiring dialysis. After transplantation, clinical and biochemical signs of porphyria disappeared. [ncbi.nlm.nih.gov]

• Convulsions

  We report a series of six cases who presented with convulsion and/or polyneuropathy early in the course of disease to highlight this fact. [ncbi.nlm.nih.gov]

  A neurologist’s “back hand” clue fueled an already burning fire in me to find out what was wrong with Jill, whose first presentations were neurological symptoms: tremors, headaches, nauseous and frequent fainting/convulsive spells beginning in sixth grade [globalgenes.org]

• Agitation

  Eleven patients had in acute attack abdominal pain, they were agitated and restless and suffered from insomnia. Besides they had various neurological signs. [ncbi.nlm.nih.gov]

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

  Pain can also affect back, legs and other sites; Nausea, vomiting, constipation; Dark urine – colour darkens to orange or red on exposure to light; Hypertension, tachycardia, and rarely, arrhythmias; Agitation, insomnia, confusion, psychosis with hallucinations [doi.org]

• Urinary Retention

  Urinary retention improved within 4 days. Hematin was imported by then from the United States. Later, 2 doses of hematin (4 mg/kg-160 mg in 20% albumin) were given via a central vein. She was maintained on physiotherapy. [ncbi.nlm.nih.gov]

  Clinical findings Abdominal colic, constipation, fever, leukocytosis, postural hypotension, peripheral neuritis, polyneuropathy, paraplegia, urinary retention, respiratory paralysis, behavioural changes and episodic psychosis (patients are often misdiagnosed [medical-dictionary.thefreedictionary.com]

  Neurologic symptoms may also develop, including flaccid paralysis, seizures, neuropsychiatric and urinary symptoms such as retention or incontinence and constipation. [doi.org]

  Urinary retention, incontinence, dysuria, and frequency may be observed. Tachycardia and hypertension, and less frequently fever, sweating, restlessness, and tremor are also observed. [diagnose-me.com]

  Patient B was a woman, 36 years of age, who was initially under the care of an orthopedic surgeon for severe back pain and was referred to a consultant physician for investigation of multiple symptoms, including urinary retention, dysuria, back pain, [clinchem.aaccjnls.org]

• Dark Urine

  A 47-year-old man presented with abdominal pain, neck stiffness, severe transient hypertension and unusually dark urine. Cerebrospinal fluid investigations and angiography confirmed the diagnosis of a subarachnoid haemorrhage. [ncbi.nlm.nih.gov]

  Obstruction of the biliary system can hinder excretion of bilirubin into the gut and simultaneously exceed the processing ability of the kidneys, leading to pale stools and dark urine. [accessmedicine.mhmedical.com]

  The patient may also complain of pruritus (itching), as a result of bile accumulation, and pale stool with dark urine, from the obstructive jaundice. [teachmesurgery.com]

  Each person’s symptoms may vary, and may be non-specific or severe, including: Pain in the upper right part of your belly (abdomen) Fever Chills Yellowing of the skin and eyes (jaundice) Nausea and vomiting Clay-colored stools Dark urine Low blood pressure [hopkinsmedicine.org]

• Dysuria

  Urinary retention, incontinence, dysuria, and frequency may be observed. Tachycardia and hypertension, and less frequently fever, sweating, restlessness, and tremor are also observed. [diagnose-me.com]

  Patient B was a woman, 36 years of age, who was initially under the care of an orthopedic surgeon for severe back pain and was referred to a consultant physician for investigation of multiple symptoms, including urinary retention, dysuria, back pain, [clinchem.aaccjnls.org]

  […] usually the first sign of an attack.[1][2] Other symptoms may include [1][2]: • Gastrointestinal issues (e.g., nausea, vomiting, constipation, diarrhea, abdominal distention, ileus) • Urinary tract issues (e.g., urinary retention, urinary incontinence, or dysuria [rarediseases.info.nih.gov]

  Urinary retention, incontinence, and dysuria may be present. Peripheral neuropathy is predominantly motor and is less common now than in the past. [ncbi.nlm.nih.gov]

• Red Urine

  Abstract A 7-year-old boy demonstrating hepatosplenomegaly, mild anaemia, mild mental retardation, yellow-brown teeth and dark red urine had excessively elevated levels of urinary delta-aminolevulinic acid, porphobilinogen and uroporphyrin. [ncbi.nlm.nih.gov]

  Her mother’s history led us to suspect porphyria, so we sent a urine sample from the ED for porphobilinogen (PBG) testing. Her urine was not red at that time (on further questioning, she remembered she had had an episode of “red urine” recently). [mdedge.com]

  With the block in heme synthesis at the PBG deaminase reaction the resulting in increases in ALA and PBG synthesis leads to marked increases in urinary excretion of both compounds resulting in deep red urine, a hallmark of AIP. [themedicalbiochemistrypage.org]

  URINARY SYSTEM SYMPTOMS Dark-colored urine Red urine Other common AIP symptoms Symptoms can also occur in many different areas of your body during an AIP attack. These AIP symptoms are also common in other conditions. [panhematin.com]

• Urinary Incontinence

  Meanwhile, she developed flaccid quardriparesis with urinary incontinence and bulbar palsy. Her brain MRI was normal. Her nerve conduction study was suggestive of motor radiculoneuropathy. Specific treatment for severe porphyric crisis was planned. [ncbi.nlm.nih.gov]

  […] tract issues (e.g., urinary retention, urinary incontinence, or dysuria) • Neurological issues (e.g., muscle weakness in the arms or legs, paralysis) • Psychiatric issues (e.g., insomnia, hysteria, anxiety, apathy or depression, phobias, psychosis, agitation [rarediseases.info.nih.gov]

To diagnose AIP it is essential to identify increased porphobilinogen and ALA (sometimes erythrocyte hydroxymethylbilane synthase enzyme) in patients’ freshly voided urine. If levels of porphobilinogen are within the normal levels (0-4 mg/L) during acute neurovisceral symptoms, porphyria can be eliminated as the cause [9] [10]. Spot urine tests are commonly used and can rapidly detect levels of porphobilinogen greater than 6 mg/L. Porphobilinogen levels in AIP patients remain elevated between attacks, however, the levels of porphobilinogen in some patients that have been symptom free for years may return to normal.

Coporphobilinogen, which arises from spontaneous polymerization of porphobilinogen, is the primary porphyrin detected in urine. Nonspecific elevation of porphyrins in urine is common and does not indicate AIP. Levels of porphyrins in stool are typically within the reference range or mildly elevated in AIP. Helpful screening tools include the Watson-Schwartz test (with Ehrlich’s aldehyde reagent), observing burgundy red discoloration in long stored urine and observation of pink colored urine after exposure to light, however, quantitative tests of porphobilinogen and ALA must be performed to verify AIP. Identification of the underlying mutation of the HMBS gene may be performed.

• Hyponatremia

  […] tendon reflexes motor stiffness/paralysis the rest of physical exam is often normal Imaging Radiographs abdominal radiography indication often initially obtained due to nonspecific nature of symptoms findings normal Studies Labs serum studies may see hyponatremia [medbullets.com]

  Neurovisceral symptoms resolved, and severe hyponatremia was corrected with IV saline solution without complications. [ncbi.nlm.nih.gov]

  He had increased urinary sodium (the excretion of sodium in urine was 257.09 mmol/24 h) at the same of hyponatremia. Chest computed tomography scan was normal. [doi.org]

• White Matter Lesions

  Magnetic resonance (MR) imaging demonstrated multiple large contrast-enhancing subcortical white matter lesions, which regressed with glucose and hematin infusions. [ncbi.nlm.nih.gov]

The goal for treatment of AIP attacks is to decrease heme synthesis and reduce levels of porphyrin precursors. Patients should stop taking any medications or drugs that may worsen their attack. Heme synthesis is inhibited by high doses of glucose, therefore, 400 grams of glucose per day may be administered for one to two days to treat mild attacks. For severe attacks that include neurologic dysfunction or attacks that don’t resolve within 36 hours, 4 mg/kg/day of hematin should be administered for 4 days. Severe pain may be treated with narcotics along with laxatives and stool softeners to prevent further constipation. Patients experiencing seizures should be given gabapentin (Neurontin) and classic antiseizure medication should be avoided because they have been shown to cause acute porphyria attacks. During attacks, patients should be placed on a carbohydrate rich diet and IV glucose should be administered to patients who cannot eat. Other medications to treat anxiety, hypertension, nausea, vomiting, tachycardia or restlessness may also be used as needed. Fluid and electrolyte levels should be monitored and balanced during attacks. Between attacks a balanced diet, rather than a carbohydrate rich diet, is recommended.

In summary, when an AIP attack is confirmed, treatment with an injection of glucose in mild cases or hematin in severe cases along with administration of carbohydrates is recommended. Triggering factors should be suppressed and symptom management, including pain, vomiting and neurological disorders should be addressed. In patients with recurrent attacks, hematin administration may be repeated. In severe cases hepatic transplant may be required although this is rare.

Approximately 60-80% of patients that have an AIP attack, do not experience subsequent attacks. However, improperly diagnosing AIP may be dangerous, particularly when treatment involves precipitating factors, such as certain medications. Patients treated for AIP, before severe nerve damage occurs, have a good prognosis and most symptoms resolve after an attack. Some patients develop chronic pain and although nerve damage and muscle weakness from attacks improve over time, this may take several months or longer to fully resolve. Avoiding precipitating factors is the best way to prevent future attacks from occurring.

AIP may be caused by a combination of a genetic defects coding for the PBGD enzyme and acquired causes that produce symptoms in some patients. The genetic cause of PBGD enzyme deficiency is an autosomal dominant mutation in the hydroxymethylbilane synthase (HMBS) gene (11q23.3) which codes for PBGD [1]. Penetrance of this mutation is very weak. Genetic causes of AIP are more common and patients with an enzyme mutation experience significantly diminished activity of PBGD by 40-60% of normal, leading to excessive porphyrins production. Chemicals that boost heme synthesis along with fasting, stress, infections or surgery are inducers of porphyria. Additionally, drugs such as phenobarbital, sulfonamides, estrogens, anti-seizure drugs, rifampin, metoclopramide and alcohol, which may increase the hepatic P450 system, are associated with porphyria. High levels of progesterone, observed in women after ovulation or during the end of the menstrual cycle, may lead to an acute attack. In some cases, no activating factors are identified. Patients with AIP have an increased risk for developing renal disease and hepatocellular carcinoma.

Most studies indicate a higher prevalence of AIP in women compared to men (ratio of 1.5-2:1 or about 80% of cases are in females). Symptoms appear in most patients after puberty and between the ages of 18 and 40 years of age. Attacks occurring outside of this timeframe are usually caused by a major provocation, such as use of phenobarbital or estrogens. In the general adult population prevalence of AIP is fairly low, ranging between 1 and 8 per 100,000 (1 per 75,000 in Europe) [1] [3], however, incidences have been reported to be much higher in psychiatric populations (210 per 100,000) [4].

AIP is caused by an autosomal dominant mutation in the HMBS gene which results in a defective PBGD enzyme [1]. PBGD in a vital enzyme in the heme biosynthetic pathway in the liver that catalyzes the conversion of porphobilinogen to hydroxymethylbilane [6]. The dysfunctional PBGD enzyme observed in AIP, leads to accumulation of porphobilinogen and amino-levulinic acid (ALA, porphyrin precursors). Neurologic damage appears to be the predominant problem with AIP which leads to central and peripheral neuropathies and psychiatric manifestations [5]. The connection between elevated porphobilinogen and ALA and acute attacks is unclear, due to the fact that most patients with the HMBS gene mutation have elevated porphyrin but are asymptomatic.

The genetic mutations observed in AIP result in marked deficiencies in the biosynthesis of the metalloporphyrin heme in the liver [6]. Free heme, detected at intracellular and extracellular levels, is degraded by heme oxygenase (HO) into carbon monoxide (CO) and bilirubin. The reasons for neurological involvement in AIP are not well understood, however, an interaction between CO and nitric oxide (NO) in enteric neurons of the internal anal sphincter may explain gastrointestinal dysfunction in some patients [7]. Other hypotheses include the direct neurotoxicity of ALA by interactions with the Gamma-Aminobutyric acid (GABA) receptor, altered tryptophan metabolism, or heme-dependent neural respiratory enzymatic deficiency in nerve cells [8]. Evidence suggests that axonal degeneration rather than demyelination of peripheral and autonomic nerve fibers is responsible. Usually the neurological effects of AIP are reversible although incomplete recovery has been reported in some cases.

Patients should avoid medications that incite porphyria (lists are available) including barbiturates, some antiepileptics, erythromycin and chloramphenicol. Alcohol consumption should be limited and low-caloric diets and fasting should be avoided. Other precipitating factors, including illicit drug use, smoking, stress, hypothermia, infection, fever and dehydration, should also be avoided. Adopting a healthy lifestyle that includes a balanced diet, prompt medical treatment and stress reduction is recommended. Iron status should be monitored in patients receiving regular heme arginate to detect iron overload. Genetic counseling may be beneficial to patients and their families to help identify susceptible individuals and their risk of developing or transmitting the disease.

Acute intermittent porphyria (AIP) is an autosomal dominant condition with low penetrance that causes defects in the heme biosynthetic pathway [1]. Affected individuals have genetic mutations leading to a deficiency in porphobilinogen deaminase (PBGD, previously called uroporphobilinogen I synthetase) synthesis or activity which causes the excessive production of porphyrin and its precursors [1]. The clinical features of AIP, which are due to effects on the central, peripheral and visceral nervous system, may develop from puberty onward but most often arise from age 20 to age 30. Patients with AIP display a spectrum of signs and symptoms that may include abdominal pain, neuropathies, constipation and mental disturbances that are often amplified by other factors, such as drugs [2]. Symptoms usually occur intermittently and can be life threatening due to neurologic complications, such as seizures and paralysis.

Management of AIP is often challenging due to the diverse manifestations of this disease and potentially fatal attacks. It is important to provide timely intervention in an attempt to resolve and prevent attacks and vigilant long-term monitoring for complications in essential. Along with treating AIP directly, addressing other conditions that may have triggered attacks, such as infection or drug use, is important.

Acute intermittent porphyria (AIP) is a dominant inherited disorder (only need diseased gene from one parent) that is the most common acute porphyria (disease associated with porphyrin build up). AIP occurs in people from every ethnic group and is more common in women than men. AIP attacks typically occur after puberty and cause a sudden onset of neurologic symptoms along with abdominal pain. Patients with AIP have a deficiency in the enzyme porphobilinogen deaminase, due to a genetic mutation, that leads to the accumulation of heme precursors (porphobilinogen and amino-levulinic acid) in the liver. Symptoms, including developmental abnormalities, may appear in childhood.

The most common symptom is abdominal pain. Gastrointestinal symptoms may also arise including nausea, vomiting, constipation and diarrhea. Some patients may experience difficulty urinating, which may result in an excessively full bladder. Neural dysfunction may lead to muscle weakness that usually starts in the shoulders and arms.

Diagnosis is achieved through testing patients urine during an attack, which will have elevated levels of porphobilinogen and amino-levulinic acid in AIP. Rapid treatment usually results in a full recovery, however, if treatment is delayed recovery may take longer and permanent nerve damage may occur. Primary therapies will aim at decreasing porphyrin levels, but physicians may also administer medications to address other symptoms, such as opioids for pain.

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