This enzyme deficiency can result in the accumulation of toxic porphyrin precursors in the body. However, the deficiency by itself is not sufficient to produce symptoms of the disease and most individuals with a HMBS gene mutation do not develop symptoms of AIP. Additional factors such as endocrine influences e. Most of these triggers are believed to stimulate increased heme production synthesis in the liver and include certain drugs, excessive alcohol consumption, fasting or dieting e. AIP is a multifactorial disorder, which means that several different factors such as genetic and environmental factors occurring in combination are necessary for developing symptoms of the disorder. The exact, underlying reasons why symptoms only develop in some individuals with the genetic mutation for AIP are not fully understood.
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This enzyme deficiency can result in the accumulation of toxic porphyrin precursors in the body. However, the deficiency by itself is not sufficient to produce symptoms of the disease and most individuals with a HMBS gene mutation do not develop symptoms of AIP. Additional factors such as endocrine influences e.
Most of these triggers are believed to stimulate increased heme production synthesis in the liver and include certain drugs, excessive alcohol consumption, fasting or dieting e.
AIP is a multifactorial disorder, which means that several different factors such as genetic and environmental factors occurring in combination are necessary for developing symptoms of the disorder.
The exact, underlying reasons why symptoms only develop in some individuals with the genetic mutation for AIP are not fully understood. There are several theories as to the underlying pathogenesis of AIP. One theory states that a specific porphyrin precursor most likely ALA is a hepatic liver neurotoxin that damages nerve tissue.
This theory is supported by the information obtained from patients who have had liver transplant, which corrects both the clinical and biochemical features of the condition.
A second theory suggests that heme deficiency in nerve cells neurons contributes to the development of symptoms. AIP manifests after puberty, especially in women due to hormonal influences. Symptoms usually come as discrete attacks that develop over two or more days. Abdominal pain, which is associated with nausea, can be severe and occurs in most cases. Sometimes the level of salt sodium and chloride in the blood decreases markedly and contributes to some of these symptoms.
The skin is not affected in AIP. AIP can be associated with a range of symptoms and physical findings that can potentially involve multiple organ systems of the body. The course and severity of attacks is highly variable from one person to another. In some cases, particularly those without proper diagnosis and treatment, the disorder can potentially cause life-threatening complications. It is important to note the highly variable nature of AIP and that affected individuals may not have all of the symptoms discussed above.
Affected individuals and parents of affected children should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. Affected individuals usually recover from an attack within days. However, if an acute attack is not diagnosed and treated promptly recovery can take much longer, even weeks or months.
Most affected individuals do not exhibit any symptoms in between episodes. Onset of attacks usually occurs in the 20s or 30s but may occur at or just after puberty. Onset before puberty is extremely rare. Attacks are much more common in women than men, probably because of the menstrual cycle hormones. Most people who inherit the gene for AIP never develop symptoms. However, experts recommend that all relatives of someone with AIP obtain testing, to determine who has the genetic trait and who does not.
Those who test positive for the trait should be educated as to measures that will help avoid attacks. A diagnosis of AIP can be difficult because most symptoms are nonspecific and occur episodically.
Diagnosis is usually based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and certain specialized tests. AIP should be suspected in individuals with unexplained abdominal pain, especially when occurring along with muscle weakness, psychological symptoms, neurological findings or unexplained hyponatraemia.
Dark or reddish urine in such individuals is also suggestive of AIP. However, absence of this feature does not exclude AIP.
On the other hand, the diagnosis of AIP and other types of Porphyria is sometimes made incorrectly in patients who do not have Porphyria at all, particularly if laboratory tests are improperly done or misinterpreted.
The finding of increased levels of delta-aminolevulinic acid ALA and porphobilinogen PBG in urine establishes that one of the acute Porphyrias is present. DNA is the material in cells that encodes all the genetic information of an individual. However, within a given family, everyone has the same mutation. When that mutation is known for one member, screening of the relatives is straightforward and can be done on DNA from saliva spit or a swab of the inside of the cheek. This is now the gold standard of diagnosis and is available through specialty labs.
Clinical Testing and Workup: Screening tests to measure the levels of the porphyrin precursor porphobilinogen PBG in urine are essential to confirm a diagnosis of acute Porphyria. Delta-aminolevulinic acid ALA excretion will also be elevated in urine samples from individuals with AIP, but measurement is less widely available and is not essential. These tests can be performed on a random spot urine sample that should be protected from light after collection and during transport to the laboratory.
In Europe the prevalence is estimated to be approximately 5. Prevalence is greatest in Sweden due to a founder effect. AIP can occur in individuals of all racial and ethnic backgrounds, although it is rarely reported in African-American individuals. Women are affected by symptomatic AIP more often than men. The disorder is most common in young or middle-aged women.
Family Testing: Molecular genetic testing is not essential to confirm a diagnosis as the porphyrin biochemical findings are characteristic. However molecular genetic testing to detect a mutation in the HMBS gene is usually required so that family members can be offered testing for this mutation.
Genetic testing is available mainly from laboratories specializing in Porphyria diagnosis. Having Children: Pregnancy is tolerated much better than was formerly believed. The minority that eventually have symptoms usually benefit from treatment. Given these considerations, most patients or individuals with "latent" Porphyria elect to have children for the same reasons as anyone else. Patients and family members who have inherited AIP should be counseled on how to limit their risk of any future acute attacks.
This should include information about AIP and what causes attacks, how to check if a prescribed medication is safe or unsafe and details of relevant patient support groups. Medications for pain, nausea and vomiting, IV hydration, and close observation are generally required. Glucose and other carbohydrates can help suppress disease activity, are given by vein or by mouth, and are part of initial treatment. Most hospitals do not stock it.
Generally, shipping will take at least 24 hours. This is avoided by slow infusion through a large caliber vein or central line. Porphyria experts at times suggest adding human albumin to the heme solution to reduce the risk of phlebitis. Heme therapy is indicated only if an acute attack of Porphyria is proven by a marked increase in urine PBG.
It may be useful also as preventive therapy for people with frequent recurrent attacks. During treatment of an attack, attention should be given to salt and water balance. Harmful drugs should be stopped. Attacks are often precipitated by low intake of carbohydrates and calories in an attempt to lose weight. Thus, dietary counseling is very important Diet and Nutrition. Premenstrual attacks often resolve quickly with the onset of menses; hormone manipulations may prevent such attacks.
The prognosis is usually good if the disease is recognized and if treatment and preventive measures are begun before severe nerve damage has occurred. Although symptoms usually resolve after an attack, some patients develop chronic pain. Nerve damage and associated muscle weakness can improve over a period of months or longer after a severe attack. Mental symptoms may occur during attacks but are usually not chronic.
The treatment of AIP is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Genetic counseling may benefit affected individuals and their families. Initial treatment steps also include stopping any medications that can potentially worsen AIP or cause an attack and ensuring proper caloric intake, which can include intravenous infusion of sufficient nutrients glucose and salt.
Carbohydrate loading in conjunction with good pain management may be sufficient for mild attacks. An acute neurovisceral attack often necessitates hospitalization and may require treatment with hematin. Panhematin almost always returns porphyrin and porphyrin precursor levels to normal values. The U. Food and Drug Administration FDA originally approved panhematin for the treatment of recurrent attacks of AIP in related to the menstrual cycle in susceptible women.
Because of its potency, it is usually given after a trial of glucose therapy and should be administered only by physicians experienced in the management of Porphyrias in a hospital setting. Treatment for AIP also includes drugs to treat specific symptoms such as certain pain medications analgesics , anti-anxiety drugs, anti-hypertensive drugs, and drugs to treat nausea and vomiting, tachycardia, or restlessness. Medications to treat any infections that may occur at the same time as an attack intercurrent infection may also be necessary.
Although many types of drugs are believed to be safe in individuals with AIP, recommendations about drugs for treating AIP are based upon experience and clinical study. Since many commonly used drugs have not been tested for their effects on Porphyria, they should be avoided if at all possible. If a question of drug safety arises, a physician or medical center specializing in Porphyria should be contacted.
A list of these institutions may be obtained from the American Porphyria Foundation see the Resources section of this report. Additional treatment for individuals undergoing an attack including monitoring fluid and electrolyte balances. For example, if individuals develop hyponatremia, which can induce seizures, they should be treated by saline infusion.
In some cases, an attack is precipitated by a low intake of carbohydrates in an attempt to lose weight. Consequently, dietary counseling is very important. Affected individuals who are prone to attacks should eat a normal balanced diet and should not greatly restrict their intake of carbohydrates or calories, even for short periods of time.
If weight loss is desired, it is advisable to contact a physician and dietitian. Premenstrual attacks often resolve quickly with the onset of menstruation. Some individuals who experience recurrent attacks may benefit from regular, prophylactic hematin infusion. This is sometimes recommended for women with severe symptoms before or during the time of their menses. 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.
Acute Intermittent Porphyria (AIP)
Despite being challenging, delivery of effective nursing care to patients with acute intermittent porphyria is a matter of utmost importance. In this paper, the diversity of symptoms and the difficult diagnosis of this condition are emphasized, and details concerning the treatment of this disorder in the intensive care unit are presented. We believe that acute intermittent porphyria should be borne in mind during performance of differential diagnosis of neurological, psychiatric, and gastroenterological disorders on patients whose routine investigation tests are normal, especially when precipitating factors exist. Intensive care measures and a multidisciplinary team approach are essential. Acute intermittent porphyria AIP is an autosomal dominant disorder caused by deficiency of porphobilinogen deaminase PBGD , which is involved in the hepatic heme biosynthesis [ 1 ]. There are three autosomal dominant acute porphyrias: AIP, variegate porphyria, and hereditary coproporphyria. Symptomatic AIP prevalence is 2 to 3 cases per , persons per year [ 3 ].
Porphyria, Acute Intermittent
Acute intermittent porphyria AIP is a rare autosomal dominant metabolic disorder affecting the production of heme resulting from a deficiency of the porphobilinogen deaminase. It is the most common of the acute porphyrias. The clinical presentation of AIP is highly variable and non-specific. The patients are typically asymptomatic, with most gene carriers having no family history because the condition had remained latent for several generations.
Acute Intermittent Porphyria
Acute intermittent porphyria, which causes abdominal pain and neurologic symptoms, is the most common acute porphyria. Symptoms may include vomiting, abdominal or back pain, weakness in arms or legs, and mental symptoms. See also Overview of Porphyrias. Acute intermittent porphyria occurs in people of all ethnic groups.
Acute Intermittent Porphyria Associated with Respiratory Failure: A Multidisciplinary Approach