Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Porphyria, Acute Intermittent”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1989

Abnormal thyroid function and hypercholesterolemia in a case of acute intermittent porphyria.

Acute intermittent porphyria is a genetic hepatic porphyria characterized by acute gastrointestinal and neurological symptoms, and accompanied by excess excretion of delta-aminolevulinic acid and porphobilinogen. Here, we report a case of acute intermittent porphyria with attacks of abdominal pain, an elevated serum thyroxine level, and hypercholesterolemia with an increased level of high-density lipoprotein-cholesterol concentration. The diagnosis of acute intermittent porphyria was confirmed by a high urinary excretion of porphobilinogen and a low level of erythrocyte hydroxymethylbilane synthase activity. After being treated with a high carbohydrate intake and propranolol, the patient improved gradually during the following 3 weeks. The patient remained asymptomatic during the 6-month follow-up period. The serum thyroxin and cholesterol levels returned to normal 6 months later. In conclusion, we suggest that for any patient who presents with unexplained abdominal pain, abnormal thyroid function and hypercholesterolemia, a simple Watson-Schwartz urine test should be performed for the screening of acute intermittent porphyria. If the Watson-Schwartz test is positive, the erythrocyte hydroxymethylbilane synthase activity should be determined to confirm the diagnosis of acute intermittent porphyria.

Acute Disease↗
PubMed1986

[Peridural anesthesia with procaine and fentanyl in a parturient with acute intermittent porphyria].

Acute intermittent porphyria is one of three severe hepatic porphyrias. Clinical manifestations include intermittent acute attacks of abdominal pain and neuropathy with an occasionally outcome. These attacks are often precipitated by endogenous (menstrual cycle and pregnancy in women) or exogenous factors (porphyrinogenic drugs). An epidural analgesia was performed during the labour of a pregnant woman with acute intermittent porphyria just after an acute attack of abdominal pain. Analgesia was obtained using procaine and fentanyl. The choice of drugs was based on available clinical reports and experimental studies of the porphyrinogenicity of drugs in animal models (rat in vivo and chick embryo in ovo).

Acute Disease↗
PubMed1999

Psychotropic drugs in acute intermittent porphyria.

Acute intermittent porphyria is one of a group of metabolic diseases called the porphyrias that may lead to symptoms of the central nervous system during an acute exacerbation. Certain drugs such as barbiturates are known to precipitate attacks of acute intermittent porphyria, but unfortunately there is little information regarding the safety of many psychotropic drugs in this disorder, especially the newer antidepressants and atypical antipsychotics. We report a case of an elderly patient with acute intermittent porphyria who was treated with a variety of psychotropic agents for a severe depression with psychotic features. Although many of the agents did not improve the psychiatric status of the patient, all the drugs were tolerated without precipitating an episode of acute intermittent porphyria. To our knowledge, this is the first report of the safe use of sertraline, venlafaxine, olanzapine, risperidone, clozapine, buspirone, trazodone, lorazepam, and clonazepam in a patient with documented acute intermittent porphyria. Our report also supports the safety of trifluoperazine. Although response and sensitivity to drugs may vary greatly among patients with this disorder, clinicians may want to consider the possibility of the above drugs to treat psychiatric symptoms in patients with acute intermittent porphyria.

Antidepressive Agents↗
PubMed2001

The tolerability of newer immunosuppressive medications in a patient with acute intermittent porphyria.

Acute intermittent porphyria results from a deficiency of the porphobilinogen deaminase enzyme of heme biosynthesis and is commonly exacerbated by a wide variety of medications. When referred a patient with acute intermittent porphyria for a renal transplant, only steroids and azathioprine were discovered as safe in patients with acute intermittent porphyria. The administration of many newer immunosuppressive medications, including calcineurin inhibitors, has not been documented in acute intermittent porphyria. Actually, cyclosporine is presently considered contraindicated in acute intermittent porphyria. To determine if calcineurin inhibitors would be tolerated in acute intermittent porphyria, cyclosporine and tacrolimus were administered pretransplant and were documented not to exacerbate acute intermittent porphyria. A successful renal transplant was then performed using tacrolimus. This is the first reported patient with documented acute intermittent porphyria to tolerate safely several of the newer immunosuppressive medications, including tacrolimus, mycophenolate, and rabbit antithymocytic globulin following renal transplantation. This patient's pretransplant evaluation also suggested that cyclosporine may be safe for some patients with acute intermittent porphyria.

Cyclosporine↗
PubMed1991

Identification of the most common mutation within the porphobilinogen deaminase gene in Swedish patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a metabolic disorder characterized by a partial deficiency of the porphobilinogen deaminase (PBGD, EC 4.3.1.8) activity. Previous haplotype analysis combined with genealogical data suggested a common origin of the PBGD gene mutation in the AIP families originating from northern Sweden (Lappland), where the highest prevalence of the disease (1 in 1500) is observed. An AIP family from Lappland consisting of two patients and two unaffected subjects was investigated. The genomic DNA fragments of the PBGD gene were amplified by polymerase chain reaction (PCR) and directly sequenced, and the sequence of the coding region was compared with the normal sequence to identify the mutation. A base substitution, G to A, in exon 10 of the PBGD gene was identified. The mutation changes the codon for Trp198 to a stop codon (nonsense mutation) and creates a recognition site for the restriction enzyme Nhe I. Screening of 33 Swedish AIP families showed that 15 had this mutation. Genealogical data revealed that 12 of the 15 families were related to the northern family. This finding supports the hypothesis of a "founder effect" of the mutation in the families originating from Lappland. In addition, a method is described for detection of specific sequences in the genome by one-sided PCR using Taq polymerase. This method is simple, fast, and economical and can be substituted for hybridization analysis using allele-specific oligonucleotides.

Base Sequence↗
PubMed1997

Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.

Acute intermittent porphyria (AIP) is the major autosomal dominant form of acute hepatic porphyrias. The disease is due to mutations in the gene encoding for porphobilinogen (PBG) deaminase and is characterized by life-threatening neurovisceral attacks, often precipitated by drugs, fasting, cyclical hormonal changes, or infectious diseases. This report describes a prospective study on the molecular epidemiology of PBG deaminase gene defects in AIP. It uses a sensitive, reliable, and easy-to-handle method for routine AIP molecular diagnosis and family study based on an exon-by-exon denaturing gradient gel electrophoresis (DGGE) strategy followed by direct sequencing. Fifteen genomic DNA fragments, including all the coding sequence and covering 3.35 kb of the PBG deaminase gene, were investigated in 405 subjects from 121 unrelated French Caucasian AIP families who had not been screened previously at the DNA level. PBG deaminase gene mutations were identified in 109 families, but only 78 were of different type, and each of them had a prevalence rate < 5%. Among these mutations, 33 had not been published previously. Sixty percent of these 78 mutations were located in only three exons (exons 10, 12, and 14), 44% were missense, 18% were splice defect, 19% were frameshift, and 16% were nonsense. In addition, two de novo mutational events were characterized. The evaluation of the efficiency of the standard PBG deaminase enzymatic screening method for gene-carrier detection indicated 95% of concordancy with the molecular-based diagnosis.

Base Sequence↗
PubMedDate not supplied

[Acute intermittent porphyria].

Acute intermittent porphyria is an inherited disease caused by genetic deficiency of enzyme prophobilinogen deaminase, which stopped heme synthesis. It is characterized by overproduction, accumulation and excretion of heme precursors. The authors present a young woman with clinical signs and symptoms of disease, treated successfully with heme-arginate, a newly synthetized drug in clinical use since 1985.

Adolescent↗
PubMed2000

A novel mutation in a family with non-erythroid variant form of acute intermittent porphyria.

Acute intermittent porphyria (AIP), an autosomal dominant disorder, is divided into two forms, the classical form (more than 95%) and the non-erythroid variant form, according to erythroid porphobilinogen deaminase (PBGD) activity. In the variant form, the PBGD activity is essentially normal. Detection of presymptomatic mutation carriers relies on a DNA test. This variant form of AIP is very rare, with only nine families carrying five different mutations reported in the literature. Here we report a novel G-to-T transversion in the first position of intron 1 of the PBGD gene in a family with this variant form of AIP. We also review all previously reported cases and propose an effective diagnostic approach.

Adult↗
PubMed1998

Acute intermittent porphyria.

Acute intermittent porphyria (AIP) is transmitted as an autosomal dominant disorder with incomplete penetrance. Recent population studies suggest that the prevalence of asymptomatic heterozygotes for a mutant AIP gene may be in the range of 1 in 2,000. Clinical manifestations include abdominal pain and neurological dysfunctions. These symptoms occur during acute attacks, which are often precipitated by drugs, alcohol, low caloric intake, or infections. Biochemical abnormalities are thought to result from primary defects of porphobilinogen deaminase (PBGD; also called hydroxymethyl bilane synthase), the third enzyme of the heme synthesis pathway, and consecutive hepatic overexpression of the first enzyme of the pathway, 5-aminolevulinate synthase. As a result of these enzymatic disturbances, heme precursors are synthesized in excess in the liver, and massive amounts of compounds upstream of the enzymatic block are excreted in urine. Although the pathophysiology of the disease has not yet been fully elucidated, a specific treatment of acute attacks with heme has improved the prognosis. The cDNAs and the gene encoding PBGD have been isolated, permitting identification of mutations that account for the corresponding enzymatic deficiencies. Consequently, DNA analysis improves the accuracy of detection of presymptomatic heterozygotes in AIP families, permitting better counseling.

Humans↗
PubMed1995

De-novo mutation and sporadic presentation of acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a low-penetrant autosomal dominant disorder characterised by life-threatening neurovisceral attacks, often precipitated by drugs. Prognosis is improved by presymptomatic diagnosis and counselling. We found that 29 of 103 (28%) unrelated patients presented as sporadic cases. One patient had a de-novo mutation. The same mutation has arisen de novo at least three times in 12% of British AIP families. About 3% (95% CI 1-8%) of all AIP index cases may have de-novo mutations. These findings emphasise the high frequency of sporadic presentation of AIP and indicate the limitations of presymptomatic diagnosis as an aid to management.

Base Sequence↗
PubMedDate not supplied

Identification of a prevalent nonsense mutation (W283X) and two novel mutations in the porphobilinogen deaminase gene of Swiss patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by decreased activity of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthetic pathway. We report the first molecular analysis of PBGD gene mutations in AIP patients of Swiss origin. The PBGD gene of 18 Swiss AIP patients was analyzed by denaturing gradient gel electrophoresis screening of the genomic DNA and direct sequencing. Thirteen of the 18 patients (72%) carried a nonsense mutation G(849)-->A, W283X. In addition, 4 different mutations including 2 novel mutations (Q217L and Q292X), were identified in the 5 remaining AIP patients originating from both German- and Italian-speaking regions of Switzerland.

DNA Mutational Analysis↗
PubMedDate not supplied

Detection of four novel mutations in the porphobilinogen deaminase gene in French Caucasian patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder characterized by alterations of the gene encoding porphobilinogen deaminase (PBGD: EC 4.3.1.8), the third enzyme of the heme biosynthetic pathway. The molecular heterogeneity of the mutations causing AlP has been demonstrated with a reported predominance of single base substitutions resulting in amino acid changes. The molecular basis of AIP in four French patients was investigated using denaturing gradient gel electrophoresis followed by direct sequencing. We describe four different novel mutations that affected exon 12 (a frameshift and an exon skipping), exon 4 (a stop codon) and exon 15 (a frameshift inducing a stop codon). This study further documents the molecular heterogeneity of mutations in the PBGD gene in the French Caucasian population and reports types of mutations relatively uncommon in AIP.

Electrophoresis↗
PubMed1995

A point mutation, C to T, in exon 8 of the porphobilinogen deaminase gene in a Japanese family with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a deficiency of porphobilinogen deaminase (PBGD). To date, only two mutations have been reported in Japanese patients. We report here another mutation of the gene in a Japanese patient. Analysis of the PCR amplified DNA fragments of the gene by direct-sequencing method revealed the gene abnormality responsible for the disease. The mutation found was a point mutation, C to T, in exon 8 of the gene at position 346 of the housekeeping cDNA from the translation codon ATG. This mutation resulted in an Arg116 to Trp substitution. Four carriers in the family were successfully diagnosed by detecting the mutation using restriction analysis of PCR products.

Adult↗
PubMed1998

[Acute intermittent porphyria].

Acute intermittent porphyria is an autosomal dominant condition caused by a genetic defect of the deaminase gene located on the 11. chromosome. Due to this defect only 50% of the normal enzyme quantity is produced. The disease becomes manifested only in the case of increased demands on given metabolic pathway resulting in porphobilinogen accumulation and storage in the organism. Clinical pattern involves abdominal, neurologic and psychiatric symptomatology. Laboratory diagnosis is based on the detection of delta-aminolevulinic acid, porphobilinogen, uroporphyrin and coproporphyrin in the urine. Between the attacks may only the detection of porphobilinogen deaminase in erythrocytes, leukocytes and skin fibroblasts be positive. The therapy is based on infusions of 20% glucose solution and hydromineral imbalance correction. When neurologic symptoms occur it is necessary to administer hem-arginate intravenously. The case report presents almost textbook case of a young female patient suffering from the disease. (Ref. 7.)

Adult↗
PubMed1993

High prevalence of a point mutation in the porphobilinogen deaminase gene in Dutch patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a deficiency of porphobilinogen deaminase (PBGD). Up to now 14 different mutations have been described. In an effort to investigate the molecular epidemiology of AIP we have undertaken a systematic study of different exons of the PBGD gene from a large number of unrelated patients. Here, exon 8 from 82 unrelated Dutch and French AIP patients was examined using single strand confirmation polymorphism analysis (SSCP) after polymerase chain reaction (PCR) amplification. A single base mutation, C to T, at position 346 of the sequence coding for PBGD was observed in 15 Dutch families but in only 1 French family. A simple PCR assay is described to facilitate the diagnosis of this common mutation at the DNA level.

Base Sequence↗
PubMed1999

New mutations of the hydroxymethylbilane synthase gene in German patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a low-penetrant, autosomal dominant disorder caused by decreased activity of hydroxymethylbilane synthase (HMBS; MIM 176 000), the third enzyme in the heme biosynthetic pathway. We report the first molecular analysis of HMBS gene mutations in classical AIP patients of German origin. The HMBS gene of 5 German AIP patients was analysed by DGGE-screening and direct sequencing of amplified genomic DNA. Five different mutations including four novel mutations were found. Three of them are single base substitutions that affected exon 3 (R16C), exon 10 (V202L), and intron 13 (T to A, IVS13+2) The two remaining mutations are frameshifts which produce a stop codon (del GA in exon 6 and insA in exon 14). These mutations are likely to be responsible for the decrease in HMBS activity found in both erythrocytes and non-erythroid cell lines (lymphocytes). Our results demonstrate the allelic heterogeneity of HMBS mutations in AIP patients of German origin.

Adolescent↗
PubMed2000

Two deletion mutations in the hydroxymethylbilane synthase gene in two unrelated Japanese patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease caused by a decreased activity of hydroxymethylbilane synthase (HMBS). Regarding the abnormalities of the HMBS gene, many different mutations have been reported worldwide; however, few families from Japan have been studied. In this work, we investigated the presence of mutations in two unrelated Japanese patients with AIP. Mutational analysis was performed using the polymerase chain reaction-single strand conformation polymorphism (SSCP) method, followed by DNA sequencing. Reliable restriction enzyme cleavage assays were also established for the pedigree analyses. Unique SSCP patterns were noted in exons 12 and 15 of the HMBS gene. Sequencing revealed different mutations in each patient: a two-base deletion of CT at nucleotide 730-731 (730delCT), and also a two-base deletion of CA at position 982-983 (982delCA). Both of the deletion mutations lead to truncated proteins with an abnormal C-terminus, which would be expected to decrease the stability and/or activity of HMBS. Using the cleavage assays, we were able to definitively identify gene carriers in the family. This study adds a novel mutation to those that have been previously reported, and emphasizes that molecular analysis would be very useful not only for the identification of asymptomatic gene carriers in the family but also for the detection of ancestral founders in porphyria families.

Adult↗
PubMed2002

Molecular study of the hydroxymethylbilane synthase gene (HMBS) among Polish patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP), an autosomal dominant disorder of heme biosynthesis, is due to mutations in hydroxymethylbilane synthase (HMBS; or porphobilinogen deaminase, PBGD) gene. In this study, we analyzed 20 Polish patients affected by AIP and we were able to characterize seven novel mutations. A nonsense mutation (Y46X), two frameshift mutations (315delT and 552delT) and a 131bp deletion (nucleotides 992-1123) give rise to truncated proteins. A donor splice site mutation IVS12+2T>C predicts skipping of exon 12. A missense mutation (D61Y) was identified in two apparently unrelated patients with a clearly clinical indication of AIP. An inframe 3-bp deletion (278-280delTTG) results in the removal of V93 from the enzyme. In addition to the novel mutations, nine previously described HMBS gene mutations-R26H, G111R, IVS7+1G>A, R149X, R173Q, 730-731delCT, R225X, 982-983delCA and G335D-were identified in this cohort. Our results demonstrate that molecular analysis of the PBGD gene is a more reliable method comparing to enzymatic assay in the diagnosis of AIP. Although more than 170 different mutations are known to the HMBS gene so far, over 40% of all mutations identified among the Polish AIP patients of this study are novel mutations, indicating the heterogeneity of molecular defects causing AIP.

Adult↗