Floderus Y, Shoolingin- 1 Jordan P, Harper P. Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations . Porphyria, Acute Intermittent. Porfyri, akut intermittent. Engelsk definition. An autosomal dominant porphyria that is due to a deficiency of. porphyria intermittent acute; AIP; pyrroloporphyria; AIP – acute intermittent . ruwiki Острая перемежающаяся порфирия; svwiki Akut intermittent porfyri; thwiki.
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University of Washington, Seattle; September 27, ; Last Update: It is characterized clinically by life-threatening acute neurovisceral attacks of severe abdominal intfrmittant without peritoneal signs, often accompanied by nausea, vomiting, tachycardia, and hypertension. Attacks may be complicated by neurologic findings mental changes, convulsions, and peripheral neuropathy that may progress to respiratory paralysisand hyponatremia.
Acute attacks, which may be provoked by certain drugs, alcoholic beverages, endocrine factors, calorie restriction, stress, intermittan infections, usually resolve within two weeks.
Akut intermittent porfyri (AIP) – Medibas
Other long-term complications are chronic renal failure, hepatocellular carcinoma HCCand hypertension. Attacks, which are very rare before puberty, are more common in women than men. All individuals with a genetic change in the gene HMBS that predisposes to AIP are at risk of developing acute attacks; however, most never have symptoms and are said to have latent or presymptomatic AIP. With one exception 5-aminolevulinate dehydratase deficiency [ALAD]acute attacks of porphyria are associated with an increased urinary concentration of porphobilinogen PBG.
Demonstration that an increased PBG concentration is caused by AIP requires exclusion of other acute porphyrias by analysis of porphyrins in stool and plasma. Molecular genetic testing is used in a symptomatic individual to identify a pathogenic variant that can then be used to identify AIP in relatives of the proband. Assay of erythrocyte HMBS enzyme activity may be useful in families in which an HMBS pathogenic variant cannot be identified or when molecular testing is not available.
Manage together with a porphyria specialist; treatment options include ovulation suppression with gonadorelin analogues, regular hematin infusions, or as a last resort liver transplantation. Evaluation of relatives at risk: If the HMBS pathogenic variant is known in a family, at-risk relatives can benefit from molecular genetic testing to clarify their genetic status, so that those at increased risk of developing acute attacks of AIP can be identified early and counseled about preventive measures.
Prevention of primary manifestations: All individuals with latent porphyria, the parents of affected individuals, and patients in remission should be advised about measures that diminish the risk of acute attacks:. Prevention of secondary complications: Patients treated regularly with heme arginate require monitoring of iron status to detect iron overload. Individuals who have experienced acute attacks require monitoring of renal function; in some countries annual hepatic imaging to detect HCC is also offered to all individuals with an HMBS pathogenic variant after age 50 years whether or not they have experienced acute attacks.
AIP is inherited in an autosomal dominant manner. Prenatal testing is possible but is rarely requested because of the low clinical penetrance and favorable clinical outcome for the great majority of symptomatic adults. Evidence of an increased concentration of PBG in urine, using a specific quantitative assay, is essential to establish an unequivocal diagnosis of acute porphyria in a symptomatic individual.
ACUTE INTERMITTENT PORPHYRIA IN CATALONIA (SPAIN) | European Porphyria Network
View in own window. PBG concentrations decrease during remission but may remain increased for months or years. ALA is often measured with PBG by specialist laboratories but does not appear to provide any significant additional diagnostic information in uncomplicated AIP see Differential Diagnosis.
Increase mainly indicates in vitro condensation of PBG to uroporphyrins. Total urinary porphyrin, but not PBG, concentration may be increased in various disorders, including alcohol abuse and liver disease [ Badminton et al ].
The increase may be large if an analytic method that includes ether-insoluble porphyrins, e. Excludes hereditary coproporphyria see Differential Diagnosis. Plasma porphyrin concentration is usually increased during an acute attack. Plasma porphyrin fluorescence emission scanning excludes variegate porphyria if the peak is at less than nm see Differential Diagnosis.
Determination of PBG in urine. Testing is best performed on a random urine sample, protected from light prior to analysis. Thus, increased urinary PBG excretion does not necessarily confirm that symptoms are the result of porphyria.
Note that a minimum two-fold increase in urinary PBG concentration above the baseline for that individual is consistent with symptoms due to AIP [ Aarsand et al ]; however, in practice, baseline information is rarely available.
Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants. The ability of the test porfiti used to detect a pathogenic variant that is present in the indicated gene. Sequence analysis detects variants that are benign, intermitttant benign, of uncertain significancelikely pathogenic, or pathogenic.
For issues to consider in interpretation of sequence analysis results, click here. To confirm the diagnosis in a proband. The diagnosis of AIP in a symptomatic individual is based on increased PBG in a random urine sample protected from light prior to analysistogether with evidence of a normal total fecal porphyrin or normal coproporphyrin isomer ratio, and plasma porphyrin fluorescence emission scan that is either normal or shows a peak emission around nm.
Molecular genetic testing is not required to confirm the diagnosis in a symptomatic individual but may help to confirm or refute a previous diagnosis of overt AIP in an individual who is in full clinical and biochemical remission [ Whatley et al ].
Predictive testing for at-risk asymptomatic adult family members requires poorfiri identification of the pathogenic variant in the family. Prenatal diagnosis and preimplantation genetic diagnosis PGD for at-risk pregnancies require prior identification of the pathogenic variant in the family.
Symptoms intemrittant present in akuy a minority of those with a genetic change that predisposes to acute intermittent porphyria AIP. Symptoms are more common in women than men and very rare before puberty. Onset typically occurs in the third or fourth decade [ Anderson et alElder et al ]. The course of acute attacks is highly variable within and between individuals. Affected individuals may recover from acute AIP attacks within days, but recovery from severe attacks that are not promptly recognized and treated may take weeks or months.
Clinical intermitttant of AIP is typically caused by exposure to certain endogenous or exogenous factors in most individuals, but it is not uncommon for individuals to have acute attacks akuh which no precipitating factor can be identified.
Ontermittant abdominal pain, which may be generalized or localized and not accompanied by muscle guarding, is the most common symptom and is often the initial sign of an acute attack. Back, buttock, or limb pain may be a feature. Gastrointestinal features including nausea, vomiting, constipation or diarrhea, abdominal distention, and ileus are also common.
Tachycardia and hypertension are frequent, while fever, sweating, restlessness, and tremor are seen pofriri frequently. Urinary retention, incontinence, and dysuria may be present. Peripheral neuropathy is predominantly motor and is less common now than in the past. Muscle weakness often begins proximally in the legs but may involve the arms or legs distally and can progress to include respiratory muscles resulting in complete paralysis with respiratory failure.
Bilateral axonal motor neuropathy may also involve the distal radial nerves [ King et al ].
Motor neuropathy may also affect the cranial nerves or lead to bulbar paralysis. Patchy sensory neuropathy may also occur [ Wikberg et al ]. These symptoms resolve after the attack, though anxiety may persist. The cause of hyponatremia is not clear; both SIADH syndrome of inappropriate antidiuretic hormone release and renal salt wasting have been proposed as mechanisms.
Seizures may also occur as a manifestation of central nervous system involvement of the acute attack. Attacks of acute porphyria may be precipitated by endogenous or exogenous factors [ Anderson et al ]. Mortality directly related to acute attacks is now very rare in most countries as a result of improved treatment use of human hemin and identification and counseling of presymptomatic relatives.
Deaths may occur as a complication of HCC or liver transplantation. To date, five children with homozygous HMBS pathogenic variants have been described. Two major hypotheses for the pathogenesis of the neurologic lesions that give rise to the clinical features of acute porphyria have been proposed: However, the success of liver transplantation as a cure for recurrent acute attacks [ Soonawalla et al ] and the transplant of a liver from persons with AIP into unaffected persons who then experienced acute attacks [ Dowman et al ] clearly implicate release of a hepatic neurotoxin, probably ALA, as their cause.
The penetrance for clinical manifestations of an HMBS pathogenic variant is not accurately known. The minimum prevalence of disease-specific HMBS variants in France is per million inhabitants [ Nordmann et al ]. The penetrance of overt AIP in France was recently reported as 5. In most countries AIP is the most common of the acute hepatic porphyrias [ Anderson et alPuy et al ]. Clinically indistinguishable acute neurovisceral attacks occur in acute intermittent porphyria AIP and the three other acute porphyrias: Lead poisoning may also mimic the symptoms and disturb heme biosynthesis; however, anemia, a feature of lead poisoning, is not a feature of AIP.
Diagnostic abnormalities are shown. See Table 1 for biochemical characteristics of clinically manifest AIP. Uroporphyrin from in vitro polymerization of PBG and coproporphyrin; measurement is not required for diagnosis and may mislead.
Plasma porphyrin concentration may occasionally be normal; fluorescence emission spectroscopy does not distinguish between HCP and AIP. Protoporphyrin is the main stool porphyrin, but a small increase in coproporphyrin III is also observed. Plasma porphyrin concentration is always increased and fluorescence emission spectroscopy distinguishes VP from all other porphyrias.
Hematuria, ingestion of beetroot, some drugs and food additives, and porphyrin excretion in other porphyrias e. To establish the extent of disease and needs in an individual diagnosed with acute intermittent porphyria AIP the following evaluations are recommended:. Immediate treatment of an acute neurovisceral attack does not require confirmation of the specific type of acute porphyria.
Peripheral cannulas used to administer hematin should be replaced after each use. Recurrent acute attacks are best managed with support and advice from a porphyria specialist.
Acute intermittent porphyria
See information and contact details of specialist porphyria centers at porphyria. Medical therapy aims to reduce the frequency and or severity of acute attacks by the following measures:. Liver transplantation is curative and reported from several centers [ Soonawalla et alWahlin et alDowman et al ].
Indications include repeated life-threatening acute attacks, failure of medical therapy, and poor quality of life [ Seth et al ]. Combined liver and kidney transplantation, which has been successful, can be considered in those with AIP with repeated severe attacks and renal failure [ Wahlin et al ]. Cimetidine has been suggested as an alternative treatment [ Rogers ]; however, evidence for clinical efficacy remains elusive.
No recent formal study has been performed, but informal feedback from experienced clinicians at international porphyria meetings indicates that few patients have benefited from this treatment.
Patients should be advised to register with an organization that provides warning jewelry in case of an accident e. Patients should be advised about support available from national patient associations where available.
Good-quality information is now widely available from patient or professional organizations either in paper form or from the Internet; see Resources.
Advice on safe treatment of persons with porphyria in some specific clinical situations e.