AIP
MCID: PRP083
MIFTS: 64

Porphyria, Acute Intermittent (AIP)

Categories: Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Porphyria, Acute Intermittent

MalaCards integrated aliases for Porphyria, Acute Intermittent:

Name: Porphyria, Acute Intermittent 56 74 13 43 39
Acute Intermittent Porphyria 12 74 24 52 58 73 29 6 15 71
Porphobilinogen Deaminase Deficiency 56 24 52 73
Pbgd Deficiency 56 24 52 73
Porphyria, Acute Intermittent, Nonerythroid Variant 56 29 6
Uroporphyrinogen Synthase Deficiency 56 52 73
Porphyria, Swedish Type 56 52 73
Ups Deficiency 56 52 73
Aip 56 52 73
Hydroxymethylbilane Synthase Deficiency 52 71
Aip - Acute Intermittent Porphyria 12
Porphyria Intermittent Acute 12
Porphyria Acute Intermittent 54
Pyrroloporphyria 12
Hmbs Deficiency 52

Characteristics:

Orphanet epidemiological data:

58
acute intermittent porphyria
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Europe),1-9/1000000 (Europe),<1/1000000 (France),1-9/1000000 (France),<1/1000000 (Italy),1-9/1000000 (Italy),<1/1000000 (Finland),1-9/1000000 (Finland),<1/1000000 (Netherlands),1-9/1000000 (Netherlands),<1/1000000 (Norway),1-9/1000000 (Norway),<1/1000000 (Poland),1-9/1000000 (Poland),<1/1000000 (Spain),1-9/1000000 (Spain),<1/1000000 (Sweden),1-5/10000 (Sweden),<1/1000000 (Switzerland),1-9/1000000 (Switzerland),<1/1000000 (United Kingdom),1-9/1000000 (United Kingdom); Age of onset: Adolescent,Adult;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
acute attacks rarely occur before puberty
attacks precipitated by drugs (e.g. barbiturates, sulfonamides), alcohol, infection, starvation, and hormonal changes
attacks more common in women
ninety percent of patients with pbg deaminase deficiency are clinically unaffected


HPO:

31
porphyria, acute intermittent:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance Families from the french reference center for porphyria were evaluated for penetrance of aip. the cohort consisted of 496 symptomatic individuals and 1672 asymptomatic relatives with an hmbs pathogenic variant. the estimated penetrance of aip in affected families was 22.9% and 12.7% in the relatives of aip index cases....

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases
Rare renal diseases
Rare skin diseases
Inborn errors of metabolism


Summaries for Porphyria, Acute Intermittent

OMIM : 56 Porphyrias are inherited defects in the biosynthesis of heme. Acute intermittent porphyria, the most common form of porphyria, is an autosomal dominant disorder characterized by recurrent attacks of abdominal pain, gastrointestinal dysfunction, and neurologic disturbances. In the classic form of AIP, both the ubiquitous 'nonerythroid' housekeeping HMBS isoform and the 'erythroid' HMBS isoform are deficient. However, about 5% of families have the 'nonerythroid variant' of AIP, with a defect only in the ubiquitous nonerythroid HMBS isoform and normal levels of the erythroid HMBS isoform. Clinical characteristics in the 2 forms are identical; diagnostic methods based on the level of enzyme in erythrocytes is ineffective (Puy et al., 1998; Petrides, 1998; Whatley et al., 2000). There are several other forms of porphyria: see porphyria cutanea tarda (176100), variegata porphyria (176200), coproporphyria (121300), acute hepatic porphyria (125270), and congenital erythropoietic porphyria (263700). (176000)

MalaCards based summary : Porphyria, Acute Intermittent, also known as acute intermittent porphyria, is related to inappropriate adh syndrome and acute porphyria, and has symptoms including seizures, vomiting and abdominal pain. An important gene associated with Porphyria, Acute Intermittent is HMBS (Hydroxymethylbilane Synthase), and among its related pathways/superpathways are Metabolism and Porphyrin and chlorophyll metabolism. The drugs Tin mesoporphyrin and Midazolam have been mentioned in the context of this disorder. Affiliated tissues include liver, skin and brain, and related phenotypes are nausea and vomiting and abdominal pain

NIH Rare Diseases : 52 Acute intermittent porphyria (AIP) is one of the liver (hepatic) porphyrias . AIP is caused by low levels of porphobilinogen deaminase (PBGD), an enzyme also often called hydroxymethylbilane synthase. The low levels of PBGD are generally not sufficient to cause symptoms; however, activating factors such as hormones , drugs, and dietary changes may trigger symptoms. Although most individuals with AIP never develop symptoms, symptomatic individuals typically present with abdominal pain with nausea. Treatment is dependent on the symptoms.

UniProtKB/Swiss-Prot : 73 Acute intermittent porphyria: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AIP is an autosomal dominant form of hepatic porphyria characterized by attacks of gastrointestinal disturbances, abdominal colic, with neurological dysfunctions, hypertension, tachycardia and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.

Wikipedia : 74 Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder affecting the... more...

GeneReviews: NBK1193

Related Diseases for Porphyria, Acute Intermittent

Diseases related to Porphyria, Acute Intermittent via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 329)
# Related Disease Score Top Affiliating Genes
1 inappropriate adh syndrome 30.3 CPOX AVP
2 acute porphyria 30.3 UROS UROD PPOX PC HMOX1 HMBS
3 porphyria 29.8 UROS UROD PPOX PC HPX HMOX1
4 siderosis 29.6 UROD HMOX1
5 porphyria, congenital erythropoietic 29.5 UROS UROD HMBS FECH CPOX ALAD
6 porphyria cutanea tarda 28.2 UROS UROD PPOX HPX HMBS FECH
7 variegate porphyria 28.2 UROS UROD PPOX HMBS FECH CPOX
8 protoporphyria, erythropoietic, 1 28.1 UROS UROD PPOX HMOX1 HMBS FECH
9 coproporphyria, hereditary 26.5 UROS UROD SLC15A2 PPOX HMBS FLVCR1
10 aip familial isolated pituitary adenomas 12.6
11 acromegaly 12.2
12 pituitary adenoma 1, multiple types 12.2
13 acute interstitial pneumonia 12.1
14 autoimmune pancreatitis 12.1
15 pituitary adenoma, prolactin-secreting 12.1
16 acth-secreting pituitary adenoma 11.9
17 adenoma 11.8
18 pituitary adenoma 11.8
19 familial isolated pituitary adenoma 11.7
20 gigantism 11.6
21 acroleukopathy, symmetric 11.6
22 pituitary tumors 11.6
23 pituitary apoplexy 11.6
24 autoimmune pancreatitis type 1 11.6
25 hormone producing pituitary cancer 11.5
26 multiple endocrine neoplasia, type i 11.5
27 inherited cancer-predisposing syndrome 11.5
28 carney complex variant 11.5
29 aminolevulinic acid dehydratase deficiency porphyria 11.5
30 growth hormone secreting pituitary adenoma 11.4
31 hepatitis b 11.4
32 multiple endocrine neoplasia, type iv 11.4
33 functioning pituitary adenoma 11.4
34 hepatitis 11.4
35 idiopathic interstitial pneumonia 11.3
36 chester porphyria 11.3
37 autoimmune pancreatitis type 2 11.2
38 cell type benign neoplasm 11.1
39 endocrine organ benign neoplasm 11.1
40 pituitary infarct 11.1
41 hyperpituitarism 11.1
42 pituitary carcinoma 11.1
43 pituitary gland disease 11.1
44 silent pituitary adenoma 11.1
45 null pituitary adenoma 11.1
46 cancer-associated retinopathy 11.1
47 multiple endocrine neoplasia 10.5
48 kidney disease 10.4
49 systemic lupus erythematosus 10.4
50 lupus erythematosus 10.4

Graphical network of the top 20 diseases related to Porphyria, Acute Intermittent:



Diseases related to Porphyria, Acute Intermittent

Symptoms & Phenotypes for Porphyria, Acute Intermittent

Human phenotypes related to Porphyria, Acute Intermittent:

58 31 (show top 50) (show all 70)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nausea and vomiting 58 31 hallmark (90%) Frequent (79-30%) HP:0002017
2 abdominal pain 58 31 hallmark (90%) Very frequent (99-80%) HP:0002027
3 anxiety 58 31 hallmark (90%) Occasional (29-5%) HP:0000739
4 depressivity 58 31 hallmark (90%) Occasional (29-5%) HP:0000716
5 insomnia 58 31 hallmark (90%) Occasional (29-5%) HP:0100785
6 urinary retention 58 31 hallmark (90%) Very rare (<4-1%) HP:0000016
7 myalgia 31 hallmark (90%) HP:0003326
8 anorexia 31 hallmark (90%) HP:0002039
9 abnormal urinary color 31 hallmark (90%) HP:0012086
10 seizure 31 hallmark (90%) HP:0001250
11 hyperhidrosis 58 31 frequent (33%) Very rare (<4-1%) HP:0000975
12 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
13 arrhythmia 31 frequent (33%) HP:0011675
14 paresthesia 31 frequent (33%) HP:0003401
15 hypertensive crisis 31 frequent (33%) HP:0100735
16 hallucinations 58 31 occasional (7.5%) Occasional (29-5%) HP:0000738
17 renal insufficiency 58 31 occasional (7.5%) Frequent (79-30%) HP:0000083
18 cranial nerve paralysis 58 31 occasional (7.5%) Frequent (79-30%) HP:0006824
19 hyponatremia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002902
20 hepatocellular carcinoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001402
21 weight loss 31 occasional (7.5%) HP:0001824
22 arthralgia 31 occasional (7.5%) HP:0002829
23 hyperlipidemia 31 occasional (7.5%) HP:0003077
24 lethargy 31 occasional (7.5%) HP:0001254
25 diaphragmatic paralysis 31 occasional (7.5%) HP:0006597
26 paraparesis 31 occasional (7.5%) HP:0002385
27 hypertension 58 31 Frequent (79-30%) HP:0000822
28 dysuria 58 31 Very rare (<4-1%) HP:0100518
29 tachycardia 58 31 Frequent (79-30%) HP:0001649
30 diarrhea 58 31 Occasional (29-5%) HP:0002014
31 urinary incontinence 58 31 Very rare (<4-1%) HP:0000020
32 elevated urinary delta-aminolevulinic acid 58 31 Very frequent (99-80%) HP:0003163
33 respiratory paralysis 58 31 Occasional (29-5%) HP:0002203
34 seizures 58 Occasional (29-5%)
35 muscle weakness 31 HP:0001324
36 vomiting 31 HP:0002013
37 fever 58 Occasional (29-5%)
38 peripheral neuropathy 58 Frequent (79-30%)
39 tremor 58 Very rare (<4-1%)
40 memory impairment 58 Occasional (29-5%)
41 respiratory insufficiency 58 Occasional (29-5%)
42 back pain 58 Frequent (79-30%)
43 proximal muscle weakness in lower limbs 58 Occasional (29-5%)
44 proximal muscle weakness in upper limbs 58 Occasional (29-5%)
45 mental deterioration 58 Frequent (79-30%)
46 restlessness 58 Occasional (29-5%)
47 sensory impairment 58 Occasional (29-5%)
48 brain imaging abnormality 58 Occasional (29-5%)
49 abdominal distention 58 Occasional (29-5%)
50 distal muscle weakness 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
anxiety
psychotic episodes
acute episodes of neuropathic symptoms
depression
more
Cardiovascular Vascular:
hypertension

Cardiovascular Heart:
tachycardia

Respiratory Lung:
respiratory paralysis

Neoplasia:
increased incidence of hepatocellular carcinoma

Abdomen Gastrointestinal:
vomiting
abdominal pain
constipation
diarrhea
nausea
more
Genitourinary Bladder:
dysuria
urinary retention
urinary incontinence

Neurologic Peripheral Nervous System:
paralysis
acute episodes of neuropathic symptoms
weakness
motor, sensory, or autonomic neuropathy

Endocrine Features:
syndrome of inappropriate antidiuretic hormone (siadh)

Laboratory Abnormalities:
erythrocyte porphobilinogen (pbg) deaminase deficiency (exception: type ii aip)
increased urinary delta-aminolevulinic acid (ala) and porphobilinogen (pbg) during acute attacks
urine occasionally port-wine in color secondary to porphobilinogen

Clinical features from OMIM:

176000

UMLS symptoms related to Porphyria, Acute Intermittent:


seizures, vomiting, abdominal pain, constipation, dysuria, diarrhea, nausea, weakness

MGI Mouse Phenotypes related to Porphyria, Acute Intermittent:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.07 ALAD ALAS2 AVP CPOX FECH FLVCR1
2 hematopoietic system MP:0005397 10.02 ALAS2 AVP CPOX FECH FLVCR1 HMBS
3 mortality/aging MP:0010768 9.8 ALAD ALAS1 ALAS2 AVP CPOX FECH
4 liver/biliary system MP:0005370 9.63 FECH HMBS HMOX1 HPX UROD UROS
5 renal/urinary system MP:0005367 9.23 AVP FLVCR1 HMBS HMOX1 HPX PPOX

Drugs & Therapeutics for Porphyria, Acute Intermittent

Drugs for Porphyria, Acute Intermittent (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 26)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Tin mesoporphyrin Phase 2
2
Midazolam Approved, Illicit Phase 1 59467-70-8 4192
3
Omeprazole Approved, Investigational, Vet_approved Phase 1 73590-58-6 4594
4
Dextromethorphan Approved Phase 1 125-71-3 5360696 5362449
5
Losartan Approved Phase 1 114798-26-4 3961
6
Caffeine Approved Phase 1 58-08-2 2519
7
Chlorpromazine Approved, Investigational, Vet_approved Phase 1 50-53-3 2726
8
Dopamine Approved Phase 1 51-61-6, 62-31-7 681
9 Liver Extracts Phase 1
10 Dopamine Agents Phase 1
11 Dopamine Antagonists Phase 1
12 Antiemetics Phase 1
13 Psychotropic Drugs Phase 1
14 Antipsychotic Agents Phase 1
15 Neurotransmitter Agents Phase 1
16 Gastrointestinal Agents Phase 1
17
Iron Approved, Experimental 15438-31-0, 7439-89-6 27284 23925
18
Aminolevulinic acid Approved 106-60-5 137
19
Isoniazid Approved, Investigational 54-85-3 3767
20
Protoporphyrin IX Experimental 553-12-8
21 Anti-Infective Agents
22 Lipid Regulating Agents
23 Antitubercular Agents
24 Anti-Bacterial Agents
25 Antimetabolites
26 Hypolipidemic Agents

Interventional clinical trials:

(show all 24)
# Name Status NCT ID Phase Drugs
1 A Multi-centre, Double-blind, Randomized, Placebo-controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Porphozym (Recombinant Human Porphobilinogen Deaminase) in the Treatment of Acute Attacks in AIP Completed NCT00418795 Phase 2, Phase 3 recombinant human porphobilinogen deaminase (Porphozym)
2 ENVISION: A Phase 3 Randomized, Double-blind, Placebo-Controlled Multicenter Study With an Open-label Extension to Evaluate the Efficacy and Safety of Givosiran in Patients With Acute Hepatic Porphyrias Active, not recruiting NCT03338816 Phase 3 Givosiran;Placebo
3 Studies in Porphyria III: Heme and Tin Mesoporphyrin in Acute Porphyrias Completed NCT00004396 Phase 2 heme arginate;tin mesoporphyrin
4 Phase I/II Study of Heme Arginate and Tin Mesoporphyrin for Acute Porphyria Completed NCT00004789 Phase 1, Phase 2 heme arginate;tin mesoporphyrin
5 Safety and Efficacy of Panhematin™ for Prevention of Acute Attacks of Porphyria Recruiting NCT02922413 Phase 2
6 A Multicenter, Open-label Extension Study to Evaluate the Long-term Safety and Clinical Activity of Subcutaneously Administered ALN-AS1 in Patients With Acute Intermittent Porphyria Who Have Completed a Previous Clinical Study With ALN-AS1 Active, not recruiting NCT02949830 Phase 1, Phase 2 givosiran (ALN-AS1)
7 A Double-blind, Randomized, Placebo-controlled, Parallel Group Trial on the Efficacy and Safety of PanhematinTM in the Treatment of Acute Attacks of Porphyria Active, not recruiting NCT02180412 Phase 2
8 A Phase 2, Open-Label, Multiple-Dose Study Investigating the Efficacy and Safety of Panhematin in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome Terminated NCT00467610 Phase 2 Panhematin
9 A Phase 1, Single-ascending Dose, Multiple-ascending Dose, and Multi-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN AS1 in Patients With Acute Intermittent Porphyria (AIP) Completed NCT02452372 Phase 1 givosiran (ALN-AS1);Sterile Normal Saline (0.9% NaCl)
10 A Drug-Drug Interaction Study to Investigate the Effect of Givosiran on the Pharmacokinetics (PK) of Midazolam, Caffeine, Losartan, Omeprazole, and Dextromethorphan in Patients With Acute Intermittent Porphyria (AIP) Who Are Asymptomatic High Excreters (ASHE) Completed NCT03505853 Phase 1 Givosiran;5-probe cocktail
11 Phase I, Multicentre, Open Label, Single Dose, Dose-ranging Clinical Trial to Investigate the Safety and Tolerability of a Gene Therapy rAAV2/5-PBGD for the Treatment of Acute Intermittent Porphyria Completed NCT02082860 Phase 1
12 A Single Center, Single Dose, Open-Label, Two-Period Replicate Pilot Study to Investigate Intra-subject Variability in the Bioavailability of a Formulation Containing Chlorpromazine Hydrochloride (25 mg Sugar Coated Tablets) in at Least 16 Healthy Males and Females Under Fasting Conditions Completed NCT02943213 Phase 1 Chlorpromazine Hydrochloride
13 Effect of Hemin on Heme-Oxygenase-1 Activity in Healthy Subjects Completed NCT00882804 Phase 1 Hemin infusion;placebo infusion
14 Observational Study of Acute Intermittent Porphyria Patients Completed NCT02076763
15 Clinical Diagnosis of Acute Porphyria Completed NCT01568554
16 Study of Nutritional Factors in Porphyria Completed NCT00004788
17 Evidence-based Assessment of Medication Sensitivity in Acute Hepatic Porphyria Completed NCT03906214
18 Longitudinal Study of the Porphyrias Recruiting NCT01561157
19 Acute Porphyrias: Biomarkers for Disease Activity and Response to Treatment Active, not recruiting NCT02935400 Hemin
20 Dental Health, Diet, Inflammation and Biomarkers in Patients With Acute Intermittent Porphyria(AIP) Active, not recruiting NCT01617642
21 BioTyrosin - Biomarker for the Early Diagnosis and Monitoring in Tyrosinemia Type 1 - An International, Multicenter, Epidemiological Protocol Active, not recruiting NCT03284658
22 Expanded Access Protocol of Givosiran for Patients With Acute Hepatic Porphyria (AHP) Available NCT04056481 Givosiran
23 INSIGHT-AHP: A Study to Characterize the Prevalence of Acute Hepatic Porphyria (AHP) in Patients With Clinical Presentation and History Consistent With AHP Terminated NCT03547297
24 Quantification of the Effects of Isoniazid Treatment on Erythrocyte and Plasma Protoporphyrin IX Concentration and Plasma Aminolevulinic Acid in Patients With Erythropoietic Protoporphyria Terminated NCT01550705 Isoniazid

Search NIH Clinical Center for Porphyria, Acute Intermittent

Inferred drug relations via UMLS 71 / NDF-RT 50 :


Chlorpromazine
Chlorpromazine hydrochloride
Hemin

Cochrane evidence based reviews: porphyria, acute intermittent

Genetic Tests for Porphyria, Acute Intermittent

Genetic tests related to Porphyria, Acute Intermittent:

# Genetic test Affiliating Genes
1 Acute Intermittent Porphyria 29 HMBS
2 Porphyria, Acute Intermittent, Nonerythroid Variant 29

Anatomical Context for Porphyria, Acute Intermittent

MalaCards organs/tissues related to Porphyria, Acute Intermittent:

40
Liver, Skin, Brain, Kidney, Testes, Thyroid, Cerebellum

Publications for Porphyria, Acute Intermittent

Articles related to Porphyria, Acute Intermittent:

(show top 50) (show all 1725)
# Title Authors PMID Year
1
Identification of the most common mutation within the porphobilinogen deaminase gene in Swedish patients with acute intermittent porphyria. 61 54 6 56 24
1961762 1991
2
Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias. 24 6 56 61
15534187 2004
3
Homozygous acute intermittent porphyria in a 7-year-old boy with massive excretions of porphyrins and porphyrin precursors. 24 6 56 61
14970743 2004
4
A point mutation G----A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria. 56 24 6 61
2789372 1989
5
Non-erythroid form of acute intermittent porphyria caused by promoter and frameshift mutations distant from the coding sequence of exon 1 of the HMBS gene. 61 6 54 56
11071386 2000
6
Exon 1 donor splice site mutations in the porphobilinogen deaminase gene in the non-erythroid variant form of acute intermittent porphyria. 6 56 54 61
9860299 1998
7
Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene. 6 61 54 56
7757070 1995
8
Demystification of Chester porphyria: a nonsense mutation in the Porphobilinogen Deaminase gene. 61 6 56
17298217 2006
9
Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. 54 56 61 24
12372055 2002
10
Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis. 6 56 61
10343207 1998
11
Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria. 61 56 6
9199558 1997
12
Homozygous acute intermittent porphyria: compound heterozygosity for adjacent base transitions in the same codon of the porphobilinogen deaminase gene. 6 56 61
1577472 1992
13
Tissue-specific splicing mutation in acute intermittent porphyria. 61 56 6
2563167 1989
14
Chester porphyria: biochemical studies of a new form of acute porphyria. 61 56 6
2864531 1985
15
Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria. 61 56 24
30726693 2019
16
Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations. 56 54 61
19934113 2010
17
Ancestral founder of mutation W283X in the porphobilinogen deaminase gene among acute intermittent porphyria patients. 6 54 61
12566739 2002
18
Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation. 6 54 61
10494093 1999
19
Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations. 54 61 56
10453740 1999
20
Insertion of Alu element responsible for acute intermittent porphyria. 54 61 6
10408772 1999
21
Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria. 56 54 61
8563760 1996
22
Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes "variant acute intermittent porphyria" with normal expression of the erythroid-specific enzyme. 6 61 54
7962538 1994
23
Detection of eleven mutations causing acute intermittent porphyria using denaturing gradient gel electrophoresis. 61 54 6
8270254 1994
24
Two new mutations in the porphobilinogen deaminase gene and a screening method using PCR amplification of specific alleles. 6 61 54
8270256 1994
25
Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene. 54 56 61
7866402 1994
26
Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria. 54 6 61
8262523 1993
27
Acute intermittent porphyria caused by an arginine to histidine substitution (R26H) in the cofactor-binding cleft of porphobilinogen deaminase. 61 54 6
8401516 1993
28
High prevalence of a point mutation in the porphobilinogen deaminase gene in Dutch patients with acute intermittent porphyria. 54 6 61
8096492 1993
29
CRIM-positive mutations of acute intermittent porphyria in Finland. 61 6 54
1301948 1992
30
Linkage disequilibrium between DNA polymorphisms within the porphobilinogen deaminase gene. 56 61 54
1973402 1990
31
Haplotyping of the human porphobilinogen deaminase gene in acute intermittent porphyria by polymerase chain reaction. 54 61 56
2303246 1990
32
Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria. 61 56
30639047 2019
33
Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver. 56 61
29498764 2018
34
An update of clinical management of acute intermittent porphyria. 56 61
26366103 2015
35
Urinary excretion of porphyrins, porphobilinogen and δ-aminolaevulinic acid following an attack of acute intermittent porphyria. 56 61
23908454 2014
36
Diagnostic strategies for autosomal dominant acute porphyrias: retrospective analysis of 467 unrelated patients referred for mutational analysis of the HMBS, CPOX, or PPOX gene. 24 54 61
19460837 2009
37
Neurological manifestations of acute intermittent porphyria. 24 54 61
19268005 2009
38
Acute Intermittent Porphyria 6 61
20301372 2005
39
Liver transplantation as a cure for acute intermittent porphyria. 61 56
15001330 2004
40
Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families. 61 6
9225970 1997
41
Increased delta aminolevulinic acid and decreased pineal melatonin production. A common event in acute porphyria studies in the rat. 61 56
8550820 1996
42
Acute intermittent porphyria caused by a G to C mutation in exon 12 of the porphobilinogen deaminase gene that results in exon skipping. 61 6
8262514 1993
43
Evidence for involvement of a second genetic locus on chromosome 11q in porphyrin metabolism. 56 54
8340112 1993
44
High frequency of mutations in exon 10 of the porphobilinogen deaminase gene in patients with a CRIM-positive subtype of acute intermittent porphyria. 6 61
1496994 1992
45
Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA. 6 61
1427766 1992
46
Vincent van Gogh's illness: acute intermittent porphyria? 61 56
1773180 1991
47
Genetic heterogeneity of the porphobilinogen deaminase gene in Swedish families with acute intermittent porphyria. 56 61
1679034 1991
48
Molecular heterogeneity of acute intermittent porphyria: identification of four additional mutations resulting in the CRIM-negative subtype of the disease. 6 61
1714233 1991
49
Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria. 61 6
2243128 1990
50
Acute intermittent porphyria caused by a C----T mutation that produces a stop codon in the porphobilinogen deaminase gene. 6 61
2227955 1990

Variations for Porphyria, Acute Intermittent

ClinVar genetic disease variations for Porphyria, Acute Intermittent:

6 (show top 50) (show all 99) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HMBS NM_000190.4(HMBS):c.669_698del (p.Glu223_Leu232del)deletion Pathogenic 522578 rs1555206128 11:118963127-118963156 11:119092417-119092446
2 HMBS NM_000190.4(HMBS):c.1078_*46del (p.Ala360fs)deletion Pathogenic 549662 rs1555206402 11:118963984-118964038 11:119093274-119093328
3 HMBS NM_000190.4(HMBS):c.518G>A (p.Arg173Gln)SNV Pathogenic 1447 rs118204096 11:118962142-118962142 11:119091432-119091432
4 HMBS NM_000190.4(HMBS):c.463C>T (p.Gln155Ter)SNV Pathogenic 1448 rs118204097 11:118960940-118960940 11:119090230-119090230
5 HMBS NM_000190.4(HMBS):c.446G>A (p.Arg149Gln)SNV Pathogenic 1449 rs118204098 11:118960923-118960923 11:119090213-119090213
6 HMBS NM_000190.4(HMBS):c.734T>G (p.Leu245Arg)SNV Pathogenic 1450 rs118204099 11:118963196-118963196 11:119092486-119092486
7 HMBS NM_000190.4(HMBS):c.900del (p.His300fs)deletion Pathogenic 1451 rs1565758825 11:118963719-118963719 11:119093009-119093009
8 HMBS HMBS, 9-BP DEL, EX10deletion Pathogenic 1452
9 HMBS NM_000190.4(HMBS):c.593G>A (p.Trp198Ter)SNV Pathogenic 1453 rs118204100 11:118962217-118962217 11:119091507-119091507
10 HMBS NM_000190.4(HMBS):c.91G>A (p.Ala31Thr)SNV Pathogenic 1454 rs118204104 11:118959348-118959348 11:119088638-119088638
11 HMBS NM_000190.4(HMBS):c.100C>A (p.Gln34Lys)SNV Pathogenic 1455 rs118204105 11:118959357-118959357 11:119088647-119088647
12 HMBS NM_000190.4(HMBS):c.499C>T (p.Arg167Trp)SNV Pathogenic 1456 rs118204101 11:118962123-118962123 11:119091413-119091413
13 HMBS NM_000190.4(HMBS):c.500G>T (p.Arg167Leu)SNV Pathogenic 1457 rs118204095 11:118962124-118962124 11:119091414-119091414
14 HMBS NM_000190.4(HMBS):c.163G>T (p.Ala55Ser)SNV Pathogenic 1458 rs118204106 11:118959794-118959794 11:119089084-119089084
15 HMBS NM_000190.4(HMBS):c.174del (p.Thr59fs)deletion Pathogenic 1459 rs1565754285 11:118959804-118959804 11:119089094-119089094
16 HMBS NM_000190.4(HMBS):c.181dup (p.Asp61fs)duplication Pathogenic 1460 rs1565754296 11:118959808-118959809 11:119089098-119089099
17 HMBS NM_000190.4(HMBS):c.211-1G>ASNV Pathogenic 1461 rs1565754452 11:118959926-118959926 11:119089216-119089216
18 HMBS NM_000190.4(HMBS):c.33+1G>ASNV Pathogenic 1441 rs1565750784 11:118955777-118955777 11:119085067-119085067
19 HMBS HMBS, EX12DELdeletion Pathogenic 1442
20 HMBS NM_000190.4(HMBS):c.77G>A (p.Arg26His)SNV Pathogenic 1443 rs118204103 11:118959008-118959008 11:119088298-119088298
21 HMBS NM_000190.4(HMBS):c.33+1G>TSNV Pathogenic 1444 rs1565750784 11:118955777-118955777 11:119085067-119085067
22 HMBS NM_000190.4(HMBS):c.346C>T (p.Arg116Trp)SNV Pathogenic 1445 rs118204094 11:118960701-118960701 11:119089991-119089991
23 HMBS HMBS, 2-BP DEL, 218AGdeletion Pathogenic 1463
24 HMBS NM_000190.4(HMBS):c.331G>A (p.Gly111Arg)SNV Pathogenic 1464 rs118204107 11:118960457-118960457 11:119089747-119089747
25 HMBS NM_000190.4(HMBS):c.499-1G>ASNV Pathogenic 1465 rs1565756481 11:118962122-118962122 11:119091412-119091412
26 HMBS NM_000190.4(HMBS):c.530T>G (p.Leu177Arg)SNV Pathogenic 1466 rs118204108 11:118962154-118962154 11:119091444-119091444
27 HMBS NM_000190.4(HMBS):c.755C>T (p.Ala252Val)SNV Pathogenic 1473 rs118204114 11:118963217-118963217 11:119092507-119092507
28 HMBS NM_000190.4(HMBS):c.766C>A (p.His256Asn)SNV Pathogenic 1474 rs118204115 11:118963228-118963228 11:119092518-119092518
29 HMBS NM_000190.4(HMBS):c.771+1G>CSNV Pathogenic 1475 rs1565758008 11:118963234-118963234 11:119092524-119092524
30 HMBS HMBS, IVS14DS, G-A, +1SNV Pathogenic 1476
31 HMBS NM_000190.4(HMBS):c.266+1G>CSNV Pathogenic 1477 rs1565754565 11:118959983-118959983 11:119089273-119089273
32 HMBS NM_000190.4(HMBS):c.647G>A (p.Gly216Asp)SNV Pathogenic 1478 rs118204116 11:118962869-118962869 11:119092159-119092159
33 HMBS NM_000190.4(HMBS):c.847_848del (p.Trp283fs)deletion Pathogenic 1479 11:118963666-118963667 11:119092956-119092957
34 HMBS HMBS, ALU INSinsertion Pathogenic 1480
35 HMBS HMBS, 1-BP DEL, -154Gdeletion Pathogenic 1481
36 HMBS NM_000190.4(HMBS):c.41del (p.Asn14fs)deletion Pathogenic 1482 11:118958969-118958969 11:119088259-119088259
37 HMBS NM_000190.4(HMBS):c.849G>A (p.Trp283Ter)SNV Pathogenic 1483 rs118204117 11:118963668-118963668 11:119092958-119092958
38 HMBS NM_000190.4(HMBS):c.1A>G (p.Met1Val)SNV Pathogenic 1484 rs118204118 11:118955744-118955744 11:119085034-119085034
39 HMBS NM_000190.4(HMBS):c.242T>C (p.Leu81Pro)SNV Pathogenic 1485 rs118204119 11:118959958-118959958 11:119089248-119089248
40 HMBS NM_000190.4(HMBS):c.445C>T (p.Arg149Ter)SNV Pathogenic 1486 rs118204120 11:118960922-118960922 11:119090212-119090212
41 HMBS NM_000190.4(HMBS):c.728_729CT[1] (p.Leu244fs)short repeat Pathogenic 1468 rs1565757839 11:118963190-118963191 11:119092480-119092481
42 HMBS NM_000190.4(HMBS):c.739T>C (p.Cys247Arg)SNV Pathogenic 1469 rs118204111 11:118963201-118963201 11:119092491-119092491
43 HMBS NM_000190.4(HMBS):c.734_741dup (p.Ile248fs)duplication Pathogenic 1470 rs1565757857 11:118963191-118963192 11:119092481-119092482
44 HMBS NM_000190.4(HMBS):c.748G>A (p.Glu250Lys)SNV Pathogenic 1471 rs118204112 11:118963210-118963210 11:119092500-119092500
45 HMBS NM_000190.4(HMBS):c.160+5G>CSNV Pathogenic 694280 11:118959422-118959422 11:119088712-119088712
46 HMBS NM_000190.4(HMBS):c.583C>T (p.Arg195Cys)SNV Pathogenic 161251 rs34413634 11:118962207-118962207 11:119091497-119091497
47 HMBS NM_000190.4(HMBS):c.500G>A (p.Arg167Gln)SNV Pathogenic/Likely pathogenic 1446 rs118204095 11:118962124-118962124 11:119091414-119091414
48 HMBS NM_000190.4(HMBS):c.601C>T (p.Arg201Trp)SNV Pathogenic/Likely pathogenic 1462 rs118204109 11:118962225-118962225 11:119091515-119091515
49 HMBS NM_000190.4(HMBS):c.891dup (p.Thr298fs)duplication Likely pathogenic 617904 rs1565758795 11:118963709-118963710 11:119092999-119093000
50 HMBS NM_000190.4(HMBS):c.655G>T (p.Ala219Ser)SNV Likely pathogenic 689731 11:118963117-118963117 11:119092407-119092407

UniProtKB/Swiss-Prot genetic disease variations for Porphyria, Acute Intermittent:

73 (show top 50) (show all 89)
# Symbol AA change Variation ID SNP ID
1 HMBS p.Arg22Cys VAR_003638 rs189159450
2 HMBS p.Arg26His VAR_003639 rs118204103
3 HMBS p.Ala31Thr VAR_003640 rs118204104
4 HMBS p.Gln34Lys VAR_003641 rs118204105
5 HMBS p.Ala55Ser VAR_003642 rs118204106
6 HMBS p.Val93Phe VAR_003643
7 HMBS p.Lys98Arg VAR_003644
8 HMBS p.Gly111Arg VAR_003645 rs118204107
9 HMBS p.Arg116Gln VAR_003646 rs116504627
10 HMBS p.Arg116Trp VAR_003647 rs118204094
11 HMBS p.Pro119Leu VAR_003648
12 HMBS p.Arg149Leu VAR_003649
13 HMBS p.Arg149Gln VAR_003650 rs118204098
14 HMBS p.Arg167Gln VAR_003651 rs118204095
15 HMBS p.Arg167Trp VAR_003652 rs118204101
16 HMBS p.Arg173Gln VAR_003653 rs118204096
17 HMBS p.Arg173Trp VAR_003654 rs575222284
18 HMBS p.Leu177Arg VAR_003655 rs118204108
19 HMBS p.Arg195Cys VAR_003656 rs34413634
20 HMBS p.Arg201Trp VAR_003657 rs118204109
21 HMBS p.Val222Met VAR_003658 rs126194787
22 HMBS p.Glu223Lys VAR_003659 rs118204110
23 HMBS p.Arg225Gly VAR_003660
24 HMBS p.Leu238Arg VAR_003661
25 HMBS p.Leu245Arg VAR_003662 rs118204099
26 HMBS p.Cys247Phe VAR_003663
27 HMBS p.Cys247Arg VAR_003664 rs118204111
28 HMBS p.Glu250Ala VAR_003665
29 HMBS p.Glu250Lys VAR_003666 rs118204112
30 HMBS p.Ala252Thr VAR_003667 rs118204113
31 HMBS p.Ala252Val VAR_003668 rs118204114
32 HMBS p.His256Asn VAR_003669 rs118204115
33 HMBS p.Thr269Ile VAR_003670
34 HMBS p.Gly274Arg VAR_003671
35 HMBS p.Leu278Pro VAR_003672
36 HMBS p.Gly280Arg VAR_003673
37 HMBS p.Gly24Ser VAR_011001
38 HMBS p.Arg26Cys VAR_011002 rs998842815
39 HMBS p.Ser28Asn VAR_011003
40 HMBS p.Ala31Pro VAR_011004
41 HMBS p.Gln34Pro VAR_011005
42 HMBS p.Thr35Met VAR_011006 rs974712040
43 HMBS p.Leu42Ser VAR_011007
44 HMBS p.Asp61Asn VAR_011008
45 HMBS p.Leu85Arg VAR_011009
46 HMBS p.Val90Gly VAR_011010
47 HMBS p.Val124Asp VAR_011011
48 HMBS p.Val202Leu VAR_011013 rs914335144
49 HMBS p.Glu209Lys VAR_011014 rs100785987
50 HMBS p.Gly216Asp VAR_011015 rs118204116

Expression for Porphyria, Acute Intermittent

Search GEO for disease gene expression data for Porphyria, Acute Intermittent.

Pathways for Porphyria, Acute Intermittent

GO Terms for Porphyria, Acute Intermittent

Cellular components related to Porphyria, Acute Intermittent according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.46 PPOX FECH CPOX ALAS2
2 mitochondrial matrix GO:0005759 9.26 PC FECH ALAS2 ALAS1
3 mitochondrion GO:0005739 9.23 UROS PPOX PC FLVCR1 FECH CPOX

Biological processes related to Porphyria, Acute Intermittent according to GeneCards Suite gene sharing:

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 response to hypoxia GO:0001666 9.81 HMOX1 ALAS2 ALAS1 ALAD
2 response to ethanol GO:0045471 9.75 FECH AVP ALAD
3 cellular iron ion homeostasis GO:0006879 9.73 HPX HMOX1 FLVCR1 ALAS2
4 porphyrin-containing compound biosynthetic process GO:0006779 9.7 UROS UROD PPOX HMBS FECH CPOX
5 response to lead ion GO:0010288 9.65 FECH CPOX ALAD
6 tetrapyrrole biosynthetic process GO:0033014 9.65 UROS HMBS ALAS2 ALAS1 ALAD
7 response to arsenic-containing substance GO:0046685 9.63 FECH CPOX ALAD
8 biosynthetic process GO:0009058 9.61 ALAS2 ALAS1
9 erythrocyte development GO:0048821 9.61 ALAS2 ALAS1
10 response to iron ion GO:0010039 9.6 CPOX ALAD
11 response to metal ion GO:0010038 9.59 FECH ALAD
12 response to inorganic substance GO:0010035 9.58 CPOX ALAD
13 response to methylmercury GO:0051597 9.58 FECH CPOX ALAD
14 cellular response to arsenic-containing substance GO:0071243 9.57 UROS HMOX1
15 heme transport GO:0015886 9.56 HPX FLVCR1
16 protoporphyrinogen IX biosynthetic process GO:0006782 9.56 UROS UROD PPOX HMBS CPOX ALAS2
17 hemoglobin biosynthetic process GO:0042541 9.55 ALAS2 ALAS1
18 response to insecticide GO:0017085 9.54 FECH CPOX
19 heme metabolic process GO:0042168 9.54 UROD HPX HMOX1
20 porphyrin-containing compound metabolic process GO:0006778 9.52 ALAS2 ALAS1
21 response to platinum ion GO:0070541 9.5 UROS FECH ALAD
22 protoporphyrinogen IX metabolic process GO:0046501 9.49 PPOX FECH
23 heme biosynthetic process GO:0006783 9.28 UROS UROD PPOX HMBS FECH CPOX

Molecular functions related to Porphyria, Acute Intermittent according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.56 PC ALAS2 ALAS1 ALAD
2 lyase activity GO:0016829 9.26 UROS UROD FECH ALAD
3 heme transporter activity GO:0015232 9.16 HPX FLVCR1
4 5-aminolevulinate synthase activity GO:0003870 8.62 ALAS2 ALAS1

Sources for Porphyria, Acute Intermittent

3 CDC
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11 DGIdb
17 EFO
18 ExPASy
19 FMA
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68 SNOMED-CT via HPO
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70 Tocris
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72 UMLS via Orphanet
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