Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Acute intermittent porphyria(AIP)

MedGen UID:
56452
Concept ID:
C0162565
Disease or Syndrome
Synonyms: AIP; HMBS deficiency; Hydroxymethylbilane Synthase Deficiency; Hydroxymethylbilane synthase deficiency; Porphobilinogen deaminase deficiency; Porphyria, Swedish type; UPS deficiency; Uroporphyrinogen synthase deficiency
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
SNOMED CT: Acute intermittent porphyria (234422006); AIP - Acute intermittent porphyria (234422006); Pyrroloporphyria (234422006); Acute porphyria (234422006); Intermittent acute porphyria (234422006); Swedish porphyria (234422006); Intermittent acute porphyria syndrome (234422006)
 
Gene: HMBS
Cytogenetic location: 11q23.3
OMIM: 176000

Disease characteristics

Excerpted from the GeneReview: Acute Intermittent Porphyria
Acute intermittent porphyria (referred to as AIP in this GeneReview) results from half-normal activity of the enzyme hydroxymethylbilane synthase (HMBS). It is characterized clinically by life-threatening acute neurovisceral attacks of severe abdominal pain 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 paralysis), and hyponatremia. Acute attacks, which may be provoked by certain drugs, alcoholic beverages, endocrine factors, calorie restriction, stress, and infections, usually resolve within two weeks. Most individuals with AIP have one or a few attacks; about 5% (mainly women) have recurrent attacks (defined as >4 attacks/year) that may persist for years. Other long-term complications are chronic renal failure, hepatocellular carcinoma (HCC), and 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. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Sharon D Whatley  |  Michael N Badminton   view full author information

Additional descriptions

From OMIM
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).  http://www.omim.org/entry/176000
From GHR
Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. Heme is a vital molecule for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is a component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood). Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. Some types of porphyria, called cutaneous porphyrias, primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria, hepatoerythropoietic porphyria, and porphyria cutanea tarda. Other types of porphyria, called acute porphyrias, primarily affect the nervous system. These disorders are described as "acute" because their signs and symptoms appear quickly and usually last a short time. Episodes of acute porphyria can cause abdominal pain, vomiting, constipation, and diarrhea. During an episode, a person may also experience muscle weakness, seizures, fever, and mental changes such as anxiety and hallucinations. These signs and symptoms can be life-threatening, especially if the muscles that control breathing become paralyzed. Acute porphyrias include acute intermittent porphyria and ALAD deficiency porphyria. Two other forms of porphyria, hereditary coproporphyria and variegate porphyria, can have both acute and cutaneous symptoms. The porphyrias can also be split into erythropoietic and hepatic types, depending on where damaging compounds called porphyrins and porphyrin precursors first build up in the body. In erythropoietic porphyrias, these compounds originate in the bone marrow. Erythropoietic porphyrias include erythropoietic protoporphyria and congenital erythropoietic porphyria. Health problems associated with erythropoietic porphyrias include a low number of red blood cells (anemia) and enlargement of the spleen (splenomegaly). The other types of porphyrias are considered hepatic porphyrias. In these disorders, porphyrins and porphyrin precursors originate primarily in the liver, leading to abnormal liver function and an increased risk of developing liver cancer. Environmental factors can strongly influence the occurrence and severity of signs and symptoms of porphyria. Alcohol, smoking, certain drugs, hormones, other illnesses, stress, and dieting or periods without food (fasting) can all trigger the signs and symptoms of some forms of the disorder. Additionally, exposure to sunlight worsens the skin damage in people with cutaneous porphyrias.  http://ghr.nlm.nih.gov/condition/porphyria

Clinical features

Neoplasm of the liver
MedGen UID:
425116
Concept ID:
CN002619
Finding
The presence of a `neoplasm` (MPATH:218) of the `liver` (FMA:7197).
Urinary retention
MedGen UID:
38289
Concept ID:
C0080274
Finding
Incomplete emptying of the bladder.
Renal insufficiency
MedGen UID:
427392
Concept ID:
CN000083
Finding
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Abnormality of urine homeostasis
MedGen UID:
446471
Concept ID:
CN002804
Finding
An abnormality of the composition of urine or the levels of its components.
Dysuria
MedGen UID:
506471
Concept ID:
CN117411
Finding
Painful or difficult `urination` (GO:0060073).
Paralysis
MedGen UID:
105510
Concept ID:
C0522224
Finding
Loss of ability to move all or part of the body.
Paresthesia
MedGen UID:
505532
Concept ID:
CN003069
Finding
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Hemiplegia/hemiparesis
MedGen UID:
446595
Concept ID:
CN003873
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a severe or complete loss of strength, whereas hemiparesis refers to a relatively mild loss of strength.
Abdominal pain
MedGen UID:
505060
Concept ID:
CN001834
Finding
Pain perceived to originate in the abdomen.
Neoplasm of the liver
MedGen UID:
425116
Concept ID:
CN002619
Finding
The presence of a `neoplasm` (MPATH:218) of the `liver` (FMA:7197).
Diaphragmatic paralysis
MedGen UID:
505942
Concept ID:
CN005748
Finding
The presence of a `paralyzed` (PATO:0000763) `diaphragm` (FMA:13295).
Weight loss
MedGen UID:
504965
Concept ID:
CN001653
Finding
Reduction inexisting body weight.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Excessive sweating. In the localized type, the most frequent sites are the palms, soles, axillae, inguinal folds, and the perineal area. Its chief cause is thought to be emotional. Generalized hyperhidrosis may be induced by a hot, humid environment, by fever, or by vigorous exercise.
Tachycardia
MedGen UID:
21453
Concept ID:
C0039231
Pathologic Function
Tachyarrhythmia is any disturbance of the heart rhythm in which the heart rate is abnormally increased.
Hypertension
MedGen UID:
635666
Concept ID:
C0497247
Finding
A finding of increased blood pressure; not necessarily hypertensive disorder
Hyponatremia
MedGen UID:
6984
Concept ID:
C0020625
Pathologic Function
A disorder characterized by laboratory test results that indicate a low concentration of sodium in the blood.
Abnormality of urine homeostasis
MedGen UID:
446471
Concept ID:
CN002804
Finding
An abnormality of the composition of urine or the levels of its components.
Abnormality of lipid metabolism
MedGen UID:
428327
Concept ID:
CN002813
Finding
An abnormality in the of `lipid` (CHEBI:18059) metabolism.
Respiratory paralysis
MedGen UID:
505154
Concept ID:
CN001997
Finding
Inability to move the muscles of respiration.
Diaphragmatic paralysis
MedGen UID:
505942
Concept ID:
CN005748
Finding
The presence of a `paralyzed` (PATO:0000763) `diaphragm` (FMA:13295).
Respiratory paralysis
MedGen UID:
505154
Concept ID:
CN001997
Finding
Inability to move the muscles of respiration.
Diaphragmatic paralysis
MedGen UID:
505942
Concept ID:
CN005748
Finding
The presence of a `paralyzed` (PATO:0000763) `diaphragm` (FMA:13295).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGAcute intermittent porphyria

Recent clinical studies

Etiology

Marsden JT, Rees DC
J Clin Pathol 2014 Jan;67(1):60-5. Epub 2013 Aug 1 doi: 10.1136/jclinpath-2012-201367. [Epub ahead of print] PMID: 23908454
Casals G, Marcos J, Pozo ÓJ, Aguilera P, Herrero C, To-Figueras J
Clin Biochem 2013 Jun;46(9):819-24. Epub 2013 Mar 13 doi: 10.1016/j.clinbiochem.2013.03.001. [Epub ahead of print] PMID: 23499585
Innala E, Bäckström T, Poromaa IS, Andersson C, Bixo M
Acta Obstet Gynecol Scand 2012 Dec;91(12):1445-52. Epub 2012 Nov 1 doi: 10.1111/j.1600-0412.2012.01536.x. [Epub ahead of print] PMID: 22924787
García-Diz L, Murcia MA, Gris JL, Pons A, Monteagudo C, Martínez-Tomé M, Jiménez-Monreal AM
Eur J Clin Invest 2012 Sep;42(9):943-52. Epub 2012 Apr 21 doi: 10.1111/j.1365-2362.2012.02673.x. [Epub ahead of print] PMID: 22519672
Dowman JK, Gunson BK, Mirza DF, Bramhall SR, Badminton MN, Newsome PN; UK Liver Selection and Allocation Working Party
Liver Transpl 2012 Feb;18(2):195-200. doi: 10.1002/lt.22345. PMID: 21618697Free PMC Article

Diagnosis

Dos Santos AR, De Albuquerque RR, Doriqui MJ, Costa GC, Dos Santos AP
An Acad Bras Cienc 2013 Sep;85(3):1207-14. doi: 10.1590/S0001-37652013000300019. PMID: 24068100
Piñeiro Pauwels MB, Gerez EN, Martinez MC, Melito VA, Parera VE, Batlle A, Rossetti MV
Cell Mol Biol (Noisy-le-grand) 2013 Mar 12;59 Suppl:OL1855-60. PMID: 23522335
Innala E, Bäckström T, Poromaa IS, Andersson C, Bixo M
Acta Obstet Gynecol Scand 2012 Dec;91(12):1445-52. Epub 2012 Nov 1 doi: 10.1111/j.1600-0412.2012.01536.x. [Epub ahead of print] PMID: 22924787
Brancaleoni V, Granata F, Colancecco A, Tavazzi D, Cappellini MD, Di Pierro E
Blood Cells Mol Dis 2012 Oct 15-Dec 15;49(3-4):147-51. Epub 2012 Jun 29 doi: 10.1016/j.bcmd.2012.06.002. [Epub ahead of print] PMID: 22748422
Anyaegbu E, Goodman M, Ahn SY, Thangarajh M, Wong M, Shinawi M
J Child Neurol 2012 Jul;27(7):917-21. Epub 2011 Dec 21 doi: 10.1177/0883073811427603. [Epub ahead of print] PMID: 22190498

Therapy

Dosi RV, Ambaliya AP, Patell RD, Sonune NN
J Postgrad Med 2013 Jul-Sep;59(3):241-2. doi: 10.4103/0022-3859.118056. PMID: 24029211
Stein PE, Badminton MN, Barth JH, Rees DC, Sarkany R, Stewart MF, Cox TM
Clin Med 2012 Jun;12(3):293-4. PMID: 22783787
Anyaegbu E, Goodman M, Ahn SY, Thangarajh M, Wong M, Shinawi M
J Child Neurol 2012 Jul;27(7):917-21. Epub 2011 Dec 21 doi: 10.1177/0883073811427603. [Epub ahead of print] PMID: 22190498
Dowman JK, Gunson BK, Mirza DF, Bramhall SR, Badminton MN, Newsome PN; UK Liver Selection and Allocation Working Party
Liver Transpl 2012 Feb;18(2):195-200. doi: 10.1002/lt.22345. PMID: 21618697Free PMC Article
Mydlík M, Derzsiová K
Przegl Lek 2011;68(9):610-3. PMID: 22335011

Prognosis

Nabin A, Thapa LJ, Paudel R, Rana PV
Kathmandu Univ Med J (KUMJ) 2012 Apr-Jun;10(38):96-9. PMID: 23132486
Cojocaru IM, Sapira V, Socoliuc G, Hertea C, Balea M, Ursache C, Cojocaru M
Rom J Intern Med 2012 Jan-Mar;50(1):33-41. PMID: 22788092
Stein PE, Badminton MN, Barth JH, Rees DC, Sarkany R, Stewart MF, Cox TM
Clin Med 2012 Jun;12(3):293-4. PMID: 22783787
Dumas RP, Silva EF, Resende MA, Pantoja AV, Barros AC
Middle East J Anesthesiol 2011 Oct;21(3):405-7. PMID: 22428497
Lam CW, Lau KC, Mak CM, Tsang MW, Chan YW
Clin Chim Acta 2011 Jan 14;412(1-2):208-12. Epub 2010 Sep 17 doi: 10.1016/j.cca.2010.09.005. [Epub ahead of print] PMID: 20850424

Clinical prediction guides

Dos Santos AR, De Albuquerque RR, Doriqui MJ, Costa GC, Dos Santos AP
An Acad Bras Cienc 2013 Sep;85(3):1207-14. doi: 10.1590/S0001-37652013000300019. PMID: 24068100
Bustad HJ, Vorland M, Rønneseth E, Sandberg S, Martinez A, Toska K
Biosci Rep 2013 Aug 8;33(4) doi: 10.1042/BSR20130045. PMID: 23815679Free PMC Article
Piñeiro Pauwels MB, Gerez EN, Martinez MC, Melito VA, Parera VE, Batlle A, Rossetti MV
Cell Mol Biol (Noisy-le-grand) 2013 Mar 12;59 Suppl:OL1855-60. PMID: 23522335
Dowman JK, Gunson BK, Mirza DF, Bramhall SR, Badminton MN, Newsome PN; UK Liver Selection and Allocation Working Party
Liver Transpl 2012 Feb;18(2):195-200. doi: 10.1002/lt.22345. PMID: 21618697Free PMC Article
Lam CW, Lau KC, Mak CM, Tsang MW, Chan YW
Clin Chim Acta 2011 Jan 14;412(1-2):208-12. Epub 2010 Sep 17 doi: 10.1016/j.cca.2010.09.005. [Epub ahead of print] PMID: 20850424

Recent systematic reviews

Stein P, Badminton M, Barth J, Rees D, Stewart MF; British and Irish Porphyria Network
Ann Clin Biochem 2013 May;50(Pt 3):217-23. doi: 10.1177/0004563212474555. PMID: 23605132
Stewart MF
J Clin Pathol 2012 Nov;65(11):976-80. Epub 2012 Jul 31 doi: 10.1136/jclinpath-2012-200791. [Epub ahead of print] PMID: 22851509
Thunell S, Pomp E, Brun A
Br J Clin Pharmacol 2007 Nov;64(5):668-79. Epub 2007 Jun 19 doi: 10.1111/j.0306-5251.2007.02955.x. [Epub ahead of print] PMID: 17578481Free PMC Article
Schuurmans MM, Schneider-Yin X, Rüfenacht UB, Schnyder C, Minder CE, Puy H, Deybach JC, Minder EI
Mol Med 2001 Aug;7(8):535-42. PMID: 11591889Free PMC Article

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...