Manifestations Of Acute Intermittent Porphyria Research Articles

Reversible Cerebral Vasospasm in Acute Intermittent Porphyria: A Case Report and Review of the Literature.

The porphyrias are rare inherited diseases of heme biosynthesis which can involve the nervous system. The most common neurological manifestations of acute intermittent porphyria are autonomic visceral neuropathy, peripheral motor neuropathy, and central nervous system dysfunction. In rare cases, patients with acute intermittent porphyria have presented with cerebral infarction, suggested to be due to vasospasm in cerebral arteries. We report a case of reversible vasospasm in porphyric encephalopathy demonstrated by both magnetic resonance and conventional angiography. Unexplained abdominal pain occurred before the onset of neurological symptoms.LEARNING POINTSAcute intermittent porphyria can affect the central nervous system.Abdominal pain with neurological symptoms should prompt consideration of porphyria.Cerebral vasospasm is implicated in the pathogenesis of cerebral infarction.Heme arginate is the treatment of choice for central nervous system injury.

SIADH as the initial manifestation of acute intermittent porphyria: A case report

Acute intermittent porphyria (AIP) is a rare autosomal dominant and the most severe form of the inherited hepatic porphyrias, affecting mainly young women. We present the case of an 18-year-old female who presented with severe abdominal pain, purple urine, autonomic dysfunction, and severe hyponatremia, seizures on further evaluation came out to be a case of AIP. This case report is a reminder to keep AIP among the differentials in young female patients with a classic constellation of abdominal urine discoloration syndrome of inappropriate secretion of antidiuretic hormone and autonomic dysfunction.

Neurological Manifestations of Acute Intermittent Porphyria:Case Series and Current Review

Background: Porphyrias are a group of inherited metabolic disorders, resulting from the deficiency of specific enzyme in the hemebiosynthesis. Among these, acute intermittent porphyria (AIP) is the most common type with neuropsychiatric features encountered in the clinical practice. In this study, we describe the presentation of AIP in five different patients admitted in our hospital. Materials and Methods: We prospectively collected the data of five patients of AIP admitted in our department in the past 2 years and studied in detail the causes, precipitants, clinical presentation, diagnosis, and management of AIP. Results: All five cases were males in second to third decades of life having a history of prior gastrointestinal symptoms for variable period before presenting to us with neurological manifestations of which one had abdominal pain for 2 years and had undergone appendicectomy also. All patients had seizures and psychiatric manifestations. Four patients had axonal polyneuropathy and respiratory failure requiring prolonged ventilator support. One patient had a past and family history of AIP. Sepsis as a trigger is noted in two patients. All patients had positive urine test for porphobilinogen. All had autonomic dysfunction, hyponatremia, and three patients expired after prolonged intensive care unit stay of which two had status epilepticus. Two patients survived with complete recovery and are under regular follow-up. Conclusion: Porphyria screening should be done in all patients presenting with unexplained motor neuropathy. Avoidance of triggers, early suspicion of the acute attack, and starting treatment immediately will prevent the complications and thus reduce morbidity and mortality due to the acute attack.

Clinical characteristics of 50 patients with acute intermittent porphyria

Objective: To analyse the clinical characteristics of patients with acute intermittent porphyria (AIP) in order to improve the understanding and treatment. Methods: Patients diagnosed as AIP and admitted to the First Affiliated Hospital of Zhengzhou University were retrospectively enrolled from January 2008 to July 2018. Data of clinical manifestations, causes, laboratory data, treatment and clinical outcome were recorded. Results: Among the 50 patients, 41 patients (82%) were aged 20 to 40. The ratio of male and female was 1∶1.8. The most common symptoms were abdominal pain (94.0%), nausea, vomiting (72.0%) and constipation (42.0%). Neuropsychiatric disorders were seen in 72.0% patients, and 30.0% of the patients had dark-coloured urine. Precipitating factors included infections, menstruation, starvation, drugs, alcohol consumption, mental stimulation and so on. Laboratory tests were abnormal for urinary porphobilinogen, liver function, hyponatremia, anaemia and so on. Various mutations of hydroxymethylbilane synthase (HMBS) genes were detected in 16 patients. Management strategies included removal of risk factors, administration of glycogen and symptomatic treatment during acute episode. Most patients were discharged with improved conditions. Conclusions: The clinical manifestations of acute intermittent porphyria are complex and diverse. Misdiagnoses or malpractice may be fatal. It is critical to emphasize on its early diagnosis and treatment.

Recurrent abdominal pain as principal clinical manifestation of acute intermittent porphyria: A case report and literature review

Recurrent abdominal pain as principal clinical manifestation of acute intermittent porphyria: A case report and literature review

Pleiotropic effects of 5-aminolevulinic acid in mouse brain.

5-Aminolevulinic acid (ALA) seems to be responsible for the neuropsychiatric manifestations of acute intermittent porphyria (AIP). Our aim was to study the effect of ALA on the different metabolic pathways in the mouse brain to enhance our knowledge about the action of this heme precursor on the central nervous system. Heme metabolism, the cholinergic system, the defense enzyme system, and nitric oxide metabolism were evaluated in the encephalon of CF-1 mice receiving a single (40 mg/kg body mass) or multiple doses of ALA (40 mg/kg, every 48 h for 14 days). We subsequently found ALA accumulation in the encephalon of the mice. ALA also altered the brain cholinergic system. After one dose of ALA, a decrease in superoxide dismutase activity and a reduction in glutathione levels were detected, whereas malondialdehyde levels and catalase activity were increased. Heme oxygenase was also increased as an antioxidant response to protect the encephalon against injury. All nitric oxide synthase isoforms were induced by ALA, these changes were more significant for the inducible isoform in glial cells. In conclusion, ALA affected several metabolic pathways in mouse encephalon. Data indicate that a rapid response to oxidative stress was developed; however, with long-term intoxication, the redox balance was probably restored, thereby minimizing oxidative damage.

From Metabolism to Psychiatric Symptoms: Psychosis as a Manifestation of Acute Intermittent Porphyria

From Metabolism to Psychiatric Symptoms: Psychosis as a Manifestation of Acute Intermittent Porphyria

P01-370 - From metabolism to psychiatric symptoms: Psychosis as a manifestation of acute intermittent porphyria

Psychiatric symptoms may represent the main feature of some metabolic diseases. Acute intermittent porphyria (AIP) is the most common of the four forms of neuroporphyria. This is an heterogeneous group of hereditary illnesses with common alterations along the heme biosynthesis pathway. AIP mimics a variety of disorders, and it difficults a correct diagnosis. We report a case of confirmed diagnosis of AIP in a 19-years-old woman who was admitted to hospital due to a sudden acute psychosis. We have done also a complete bibliographic research about this illness and its relation to psychiatric symptoms.In this case the differential diagnosis included schizophrenia and substance-induced psychosis. However, the presence of abnormal abdominal pain, port-wine color urine, sensory loss and muscular weakness gave us the clue for investigate AIP. Moreover, some anamnestic details about the use of anticonceptive pills, drug abuse and starvation increased our suspicion. Given the fact that the patient and her sister were both adopted, no family history was available.The main laboratory findings supporting the diagnosis of AIP were a decrease in porphobilinogen deaminase (PBGD) activity in erythrocytes concomitantly with the detection of IVS7 (+33) G>T mutation of this enzyme’s gene.Despite the prevalence of AIP is not high around Mediterranean countries, this possibility should be kept in mind in order to elucidate the origins of a not so low number of acute psychotic episodes. They can be effectively and specifically treated, as well as easily prevented by controlling porphirinogenic factors.

Kasuistik interaktiv: Lanzarote-Urlauber mit Sepsis und Multiorganversagen – Ein langer Weg bis zur richtigen Diagnose

A forty-five year old male tourist suffers a febrile illness, delirium and severe abdominal pain on the fifth day of his holiday trip to the Canary Islands (Spain). After hospitalization he presents a surgical abdomen which requires emergency laparotomy however without detectable pathology. Progressing critical illness and septic shock leads to multiple organ failure, but focus identification is not possible. Well after return to Germany diagnostic uncertainty persists due to recurrent fever and possible travel-associated infections. Finally, besides a simple pararectal abscess, manifestation of acute intermittent porphyria is diagnosed. Clinicians should consider acute intermittent porphyria as a rare cause of a surgical abdomen. Its clinical presentation include abdominal pain, life-threatening neurovisceral, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine.

Acute Intermittent Porphyria as a Cause of Respiratory Failure: Case Report

A 45-year-old man with end-stage renal disease due to polycystic kidney disease was admitted to the hospital because of recurrent abdominal pain, progressive peripheral motor neuron neuropathy, and respiratory failure. The diagnosis of acute intermittent porphyria was confirmed by an elevated porphyrin concentration in the urine and the presence of an R167Q mutation in the porphobilinogen deaminase gene. Use of hydroxyzine, weight loss, and/or a mild upper respiratory viral infection might have been the provoking factor of the acute intermittent porphyria. Treatment with intravenous hemin (3 mg/kg) and a high-carbohydrate diet (3000 kcal/d) had no clinical effect. Tetraplegia and chronic respiratory insufficiency developed, and the patient needed a pacemaker because of a symptomatic sinus bradycardia due to autonomic dysfunction. The patient died 10 months after the first manifestation of acute intermittent porphyria.

Clinical aspects of acute intermittent porphyria in northern Sweden: A population-based study

The objective of this study was to update the clinical issues of acute intermittent porphyria (AIP), as they have not been in focus for years, and to be aware of potentially associated disorders and social consequences. A total of 356 gene carriers of AIP from northern Sweden participated in this retrospective population-based study. Eight mutations were found with a predominance of W198X (89%). Clinical manifestations of AIP (manifest AIP) were identified in 42%, 65% were women. Women were more severely stricken by AIP attacks concerning number and duration, hospital admission and early onset. Men reporting most attacks were > 40 years of age. In addition to traditional symptoms during attacks, fatigue was commonly described. Chronic AIP symptoms and disability pension due to AIP were reported in about 20% of subjects. Precipitating factors were reported with evident sex differences. Half of the gene carriers who were on medications used drugs considered not safe (in 1999), mainly antihypertensive drugs. Smoking was associated with high AIP attack frequency. Elevated levels of ALT, bile acids, creatinine, U-ALA and U-PBG and decreased levels of creatinine clearance were associated with manifest AIP. The same was true for hypertension and myalgia in the legs. Hepatoma was strikingly overrepresented. The high prevalence of manifest AIP in this study could be explained by a mutation-dependent penetrance. Our results emphasize the importance of early diagnosis, counselling and treatment of attacks, screening and treatment of associated disorders.

Use of propofol anesthesia and adjunctive treatment with levetiracetam and gabapentin in managing status epilepticus in a patient of acute intermittent porphyria

Use of propofol anesthesia and adjunctive treatment with levetiracetam and gabapentin in managing status epilepticus in a patient of acute intermittent porphyria

Kortikale Amaurosis und Status epilepticus bei akuter Porphyrie

The most common neurologic manifestations of acute intermittent porphyria (AIP) are autonomic visceral neuropathy, peripheral motor neuropathy, and CNS dysfunctions including seizures and neuropsychiatric disturbances. In rare instances, however, AIP patients have presented with acute cortical blindness. We present a 20-year-old woman who suffered her first attack of AIP. Following 1 week of abdominal pain, she was transferred from a surgical department because of sudden visual loss and deterioration of consciousness. On admission, she developed several generalized seizures. Magnetic resonance imaging showed bilateral DWI lesions occipitally and in the left anterior circulation. Cerebrospinal fluid, MR angiography, and duplex ultrasound were normal. On the following day, sedation and intubation became necessary because of a generalized status epilepticus. Analysis of porphyrinogens in blood, urine and stool showed significantly elevated values. Intravenous therapy with häm-arginate was initiated and antiepileptic therapy was changed to gagabentine. Under this therapeutical regime she remained stable and extubation was possible 48 h later.

Acute intermittent porphyria in childhood: a population‐based study

To establish age-adjusted reference intervals of urinary delta-aminolaevulinic acid (U-ALA) and porphobilinogen (U-PBG) in children, and to analyse the frequency and type of clinical manifestations of acute intermittent porphyria (AIP) in childhood. Concentrations of U-ALA and U-PBG in healthy children aged 3-16y were analysed. In a population-based study in northern Sweden of 61 children aged < 18 y with DNA-verified AIP, the clinical manifestations of AIP in childhood were analysed prospectively (up to 2.5 y). Initially the children underwent a standardized investigation (anamnesis, physical examination, laboratory tests). Instructions were issued to keep a structured diary and to provide urine samples for ALA and PBG analyses in all situations of suspected AIP attacks (prospectively). Reference intervals for U-ALA and U-PBG showed age-group variations in children. Baseline levels of U-ALA and U-PBG are increased in gene carriers, one-quarter of them exceeding the 90th percentile of age- and gender-matched controls. Baseline levels did not distinguish symptomatic from non-symptomatic children in a short-term perspective. Clinical evidence of AIP attacks was found in 10% of child AIP gene carriers; in all cases the first attack occurred before the age of 15 y. AIP symptoms in children may be vague and of short duration and U-ALA and U-PBG levels are often elevated only slightly or not at all; thus, symptoms and signs may differ from those in adults. Children of AIP gene carriers should be DNA tested, followed up and carefully instructed on preventive measures to avoid developing manifest AIP.

Acute intermittent porphyria in childhood: a population-based study

Aim: To establish age-adjusted reference intervals of urinary δ-aminolaevulinic acid (U-ALA) and porphobilinogen (U-PBG) in children, and to analyse the frequency and type of clinical manifestations of acute intermittent porphyria (AIP) in childhood. Methods: Concentrations of U-ALA and U-PBG in healthy children aged 3–16 y were analysed. In a population-based study in northern Sweden of 61 children aged >18 y with DNA-verified AIP, the clinical manifestations of AIP in childhood were analysed prospectively (up to 2.5 y). Initially the children underwent a standardized investigation (anamnesis, physical examination, laboratory tests). Instructions were issued to keep a structured diary and to provide urine samples for ALA and PBG analyses in all situations of suspected AIP attacks (prospectively). Results: Reference intervals for U-ALA and U-PBG showed age-group variations in children. Baseline levels of U-ALA and U-PBG are increased in gene carriers, one-quarter of them exceeding the 90th percentile of age- and gender-matched controls. Baseline levels did not distinguish symptomatic from non-symptomatic children in a short-term perspective. Clinical evidence of AIP attacks was found in 10% of child AIP gene carriers; in all cases the first attack occurred before the age of 15 y. Conclusion: AIP symptoms in children may be vague and of short duration and U-ALA and U-PBG levels are often elevated only slightly or not at all; thus, symptoms and signs may differ from those in adults. Children of AIP gene carriers should be DNA tested, followed up and carefully instructed on preventive measures to avoid developing manifest AIP.

Varied psychiatric manifestations of acute intermittent porphyria

Acute Intermittent Porphyria (AIP) is an autosomal dominant metabolic disorder that has various psychiatric manifestations. This is a report of a case who had six brief psychotic episodes of varying nature within a 2-month period. The psychotic manifestations included catatonic stupor, hypomania, and delirium in different episodes. The management aspects of the case have been highlighted.

Urine Concentration of 3-ethyl-5-hydroxy-4,5-dimethyl-Δ3-pyrrolin-2-one (‘Mauve Factor’) is Not Causally Related to Schizophrenia or to Acute Intermittent Porphyria

1. 3-Ethyl-5-hydroxy-4,5-dimethyl-delta 3-pyrrolin-2-one (HPL, 'mauve factor') was determined quantitatively in the urine of schizophrenic, general medical and porphyric subjects by a sensitive gas/liquid-chromatographic method using a nitrogen-specific detector. 2. A comparative evaluation with previously used methods for HPL was made and some problems of specificity are discussed. 3. The concentration of HPL in early morning and spot smaples of urine from 146 subjects with schizophrenia was not greater than that in 42 general medical patients, contrary to previous reports. 4. Of the three patients with acute intermittent porphyria, two excreted HPL. One subject, studied over a 2 year period, did so intermittently in a manner unrelated to her attacks of porphyria. 5. It is concluded that the urine content of HPL is unlikely to be causally related to schizophrenia or to the clinical manifestations of acute intermittent porphyria.

The inhibition of red cell and brain ATPase by δ-aminolaevulinic acid

Red cell membrane and brain tissue ATPase were inhibited by δ-aminolaevulinic acid. The effect was on the (Na + + K +)-dependent fraction of ATPase, and δ-aminolaevulinic acid had no effect on the magnesium-dependent fraction of ATPase. The effect of δ-aminolaevulinic acid was reversible. δ-Aminolaevulinic acid had no effect on ATPase enzyme activity on red cell ghost membranes. The difference between red cell membrane and brain tissue ATPase, on the one hand, and red cell ghost membrane ATPase on the other hand may be due to the solubility of the ATPase enzyme in the different experiments. Glycine, cysteine hydrochloride and sodium phenobarbitone had no effect on red cell membrane and brain tissue ATPase enzyme. The findings suggest a possible explanation for the neurological manifestation of acute intermittent porphyria and porphyria variegata, since the inhibition of (Na + + K +)-dependent nerve ATPase by δ-aminolaevulinic acid could block nerve conduction and cause paralysis.

Increased protein-bound iodine and thyroxine-binding globulin in acute intermittent porphyria.

SOME of the manifestations of acute intermittent porphyria are suggestive of thyrotoxicosis. These include emotional lability, tachycardia and muscular weakness, and such findings have on occasion led to thyroidectomy in acute porphyria.1 Although the patients are usually euthyroid, as shown by normal thyroidal uptake of radioiodine (RAI) and basal metabolic rate, they may be erroneously considered to have hyperthyroidism because the serum protein-bound iodine (PBI) and thyroxine iodine (total T4) are frequently increased.2 The mechanism for these increases in thyroid hormone levels in the face of apparent euthyroidism has not been elucidated and is the subject of this . . .