Acute intermittent porphyria

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Acute intermittent porphyria
Porphobilinogen.png
Porphobilinogen
Classification and external resources
Specialty endocrinology
ICD-10 E80.2
ICD-9-CM 277.1
OMIM 176000
DiseasesDB 171
eMedicine med/1880
MeSH D017118
GeneReviews

Acute intermittent porphyria (AIP) is a genetic metabolic disorder affecting the production of heme, the oxygen-binding prosthetic group of hemoglobin. It is characterized by a deficiency of the enzyme porphobilinogen deaminase, its inheritance is more commonly autosomal dominant,[1] however autosomal recessive forms of this disorder have occurred.[2] Its incidence is estimated to be between 5 and 10 in 100,000.[3]

Signs and Symptoms[edit]

Signs and symptoms of AIP can be variable. Severe and poorly localized abdominal pain is a very common symptom (found in 95% of those affected by AIP). Urinary signs and symptoms such as painful urination, urinary retention, urinary incontinence, or dark urine have also been known to occur. Psychiatric signs and symptoms of AIP may manifest as anxiety, paranoia, irritability, delusions, hallucinations, confusion, and depression.[4] Signs that suggest increased activity of the sympathetic nervous system may be evident including tachycardia, hypertension, palpitations, orthostatic hypotension, sweating, restlessness, and tremor. Other neurologic signs and symptoms of AIP include seizures, peripheral neuropathy, abnormal sensations, chest pain, leg pain, back pain or headache, and coma. Nausea, vomiting, constipation, and diarrhea can also occur. Proximal muscle weakness typically beginning in the arms is characteristic; there can be muscle pain, tingling, numbness, weakness or paralysis;[5] muscle weakness seen in AIP can progress to include the muscles of breathing causing respiratory failure and can be fatal.[citation needed]

AIP patients have an increased risk of developing hepatocellular carcinoma, melanoma, lymphoma, chronic hypertension, chronic kidney disease, and chronic pain.[6]

Pathophysiology[edit]

AIP is caused by mutations in the HMBS gene, which codes for the enzyme porphobilinogen deaminase.

A Swedish study indicated that approximately 90% of cases of acute intermittent porphyria are due to a mutation in the HMBS gene that causes decreased amounts of the enzyme, and to a lesser degree by a mutation that causes decreased activity of each enzyme molecule.[7] Under normal circumstances, heme synthesis begins in the mitochondrion, proceeds into the cytoplasm, and finishes back in the mitochondrion. However, without porphobilinogen deaminase, a necessary cytoplasmic enzyme, heme synthesis cannot finish, and the metabolite porphobilinogen accumulates in the cytoplasm.[8]

Both endogenous and exogenous factors can cause acute attacks, such as certain medications, alcohol, infections, low caloric intake, or changes in sex hormone balance during the menstrual cycle or pregnancy.[6]

Patients with AIP are commonly misdiagnosed with psychiatric diseases. Subsequent treatment with anti-psychotics increases the accumulation of porphobilinogen, thus aggravating the disease enough that it may prove fatal.[citation needed]Gene mutation located on chromosome 11q23.3. Mutations include deletions, inversions, and translations.

Diagnosis[edit]

Urine and serum show raised levels of porphobilinogen.

Assay the red blood cells for the level of porphobilinogen deaminase.

Testing[edit]

Treatment[edit]

If drugs have caused the attack, discontinuing the offending substances is essential.[citation needed]A high-carbohydrate (10% glucose) infusion is recommended, which may aid in recovery.

Hemin(Hematin)

Hematin and heme arginate is the treatment of choice during an acute attack. Heme is not a curative treatment, but can shorten attacks and reduce the intensity of an attack. Side-effects are rare but can be serious.[citation needed] Pain is extremely severe and almost always requires the use of opiates to reduce it to tolerable levels. Pain should be treated as early as medically possible due to its severity.

Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot water baths or showers may lessen nausea temporarily, but can present a risk of burns or falls.[12]

Seizures often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: Barbiturates and Primidone must be avoided as they commonly precipitate symptoms,[13] some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control.[citation needed]

Famous sufferers[edit]

One of the many hypothesized diagnoses of the artist Vincent van Gogh is that he and his siblings, in particular his brother Theo, suffered from AIP and syphilis.[14] Another theorized sufferer was King George III of the United Kingdom [15] who even had a medallion struck to commemorate his "curing". His great-great-great-great-grandson Prince William of Gloucester was reliably diagnosed with variegate porphyria in 1968.[16] It's probable that the philosopher Jean-Jacques Rousseau suffered from porphyria.[17][18][19][20]

In popular culture[edit]

  • In Season 7, Episode 9 of Scrubs, "My Dumb Luck", a patient has this disorder. J.D. diagnosed the disease when he accidentally left the patient's urine sample outside where it turned purple.
  • In Season 1, Episode 21 of CSI, "Justice is Served", a nutritionist, Dr. Susan Hillridge, has been murdering and removing the organs of her victims, after drying the organs, she grinds them and mixes the powder into protein shakes and drinks as a treatment for her porphyria.
  • In Series 4, Episode 2 of Doc Martin, "Uneasy Lies the Head", the headmaster is diagnosed with AIP after displaying erratic behavior, constipation, and a urine sample being left in a window sill and turning blue.
  • In Season 1, Episode 22 of House, M.D., "Honeymoon", House diagnoses his ex-wife's husband with AIP by testing a urine sample which he collected after stabbing a syringe into his bladder, and moving the sample closer to 2 lamps (i.e., light sources).
  • In Season 6, Episode 15 of Grey's Anatomy, "The Time Warp", Bailey reflects back on her time as an intern when she diagnosed a woman with chronic abdominal pain after numerous surgeries by other doctors.
  • In Season 1, Episode 4 of DiagnoseMe, a doctor is bedridden when she can't diagnose her own life-threatening illness.[21]
  • In Season 1, Episode 15 of Chicago Med, "Inheritance", Dr. Manning and Dr. Charles deal with a 16-year-old patient suffering from abdominal pain who adamantly refuses any drugs for fear of winding up like her drug-addicted father, this girl is later diagnosed with AIP.[22]

References[edit]

  1. ^ Whatley SD, Roberts AG, Llewellyn DH, Bennett CP, Garrett C, Elder GH (2000). "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". Hum. Genet. 107 (3): 243–8. PMID 11071386. doi:10.1007/s004390000356. 
  2. ^ Solis C, Martinez-Bermejo A, Naidich TP, Kaufmann WE, Astrin KH, Bishop DF, Desnick RJ (2004). "Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias". Archives of Neurology. 61 (11): 1764–70. PMID 15534187. doi:10.1001/archneur.61.11.1764. 
  3. ^ Diseases of Tetrapyrrole Metabolism - Refsum Disease and the Hepatic Porphyrias at eMedicine
  4. ^ Ghosh S, Chaudhury PK, Goswami HK (2006). "An analysis of six cases of acute intermittent porphyria (AIP)". Indian Journal of Psychiatry. 48 (3): 189–92. PMC 2932991Freely accessible. PMID 20844651. doi:10.4103/0019-5545.31584. 
  5. ^ http://www.mayoclinic.org/diseases-conditions/porphyria/basics/symptoms/con-20028849
  6. ^ a b Pischik E, Kauppinen R (2015). "An update of clinical management of acute intermittent porphyria". The Application of Clinical Genetics. 8: 201–14. PMC 4562648Freely accessible. PMID 26366103. doi:10.2147/TACG.S48605. 
  7. ^ Lannfelt L, Wetterberg L, Gellerfors P, Lilius L, Floderus Y, Thunell S (1989). "Mutations in acute intermittent porphyria detected by ELISA measurement of porphobilinogen deaminase". Journal of Clinical Chemistry and Clinical Biochemistry. Zeitschrift Fur Klinische Chemie Und Klinische Biochemie. 27 (11): 857–62. PMID 2607315. doi:10.1515/cclm.1989.27.11.857. 
  8. ^ Aarsand AK, Petersen PH, Sandberg S (2006). "Estimation and application of biological variation of urinary delta-aminolevulinic acid and porphobilinogen in healthy individuals and in patients with acute intermittent porphyria". Clinical Chemistry. 52 (4): 650–6. PMID 16595824. doi:10.1373/clinchem.2005.060772. 
  9. ^ Allard SA, Charles PJ, Herrick AL, McColl KE, Scott JT (1990). "Antinuclear antibodies and the diagnosis of systemic lupus erythematosus in patients with acute intermittent porphyria". Annals of the Rheumatic Diseases. 49 (4): 246–8. PMC 1004047Freely accessible. PMID 2339906. 
  10. ^ Demir, Mustafavolkan; Temiz, Tayfun; Yaylaci, Selcuk; Tamer, Ali (2014). "Acute Intermitent porphyria and early hematin treatment before confirming the diagnosis". Medical Journal of Dr. D.Y. Patil University. 7 (6): 813. doi:10.4103/0975-2870.144898. 
  11. ^ a b Stewart MF, Croft J, Reed P, New JP (2007). "Acute intermittent porphyria and phaeochromocytoma: shared features". Journal of Clinical Pathology. 60 (8): 935–6. PMC 1994495Freely accessible. PMID 17660335. doi:10.1136/jcp.2005.032722. 
  12. ^ *American Porphyria Foundation. "About Porphyria: Acute Intermittent Porhyria" Archived April 25, 2008, at the Wayback Machine., 2007,
  13. ^ Marcucci, Lisa (2004). PathCards. Baltimore, MD: Lippincott Willians & Wilkins. pp. 105–106. ISBN 978-0-7817-4399-0. 
  14. ^ Arnold, Wilfred N. Vincent van Gogh: Chemicals, Crises, and Creativity, Birkhãuser, Boston, 1992. ISBN 0-8176-3616-1.[page needed]
  15. ^ Macalpine, Ida and Hunter,Richard 'The Insanity of King George III: A Classic Case of Porphyria', British Medical Journal (1966)[page needed]
  16. ^ Rohl, John C.G. et al., Purple Secret, London: Bantam Press (1998)[page needed]
  17. ^ Bartolo Anglani, Le maschere dell'io: Rousseau e la menzogna autobiografica, Schena, 1995, pag. 113
  18. ^ "Jean-Jacques Rousseau l’errante / Letteratura e bisogni speciali 6". La Letteratura e Noi - diretto da Romano Luperini (in Italian). Retrieved 18 November 2015. 
  19. ^ "Las enfermedades de Jean-Jacques Rousseau". Revista Aleph (in Spanish). Retrieved 18 November 2015. 
  20. ^ Androutsos G, Geroulanos S (2000). "[Acute intermittent porphyria: a new hypothesis to explain Jean-Jacques Rousseau's urinary disorders]". Prog Urol. 10 (6): 1282–9. PMID 11217576. 
  21. ^ [1]
  22. ^ [2]