Mystery Monday: Have you heard of Porphyria?
Have YOU heard of Porphyria?
This week Mystery Monday is focusing on Porphyria! Thank you so much to the British Porphyria Association for the fantastic resources!
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What is Porphyria?
The Porphyrias refers to a group of conditions that result due to a disruption in the body’s pathway of making haem. Haem is an essential chemical component of many other important enzymes and molecules which interact with oxygen. Haem is present in all tissues, but is especially prominent in the bone marrow and liver. When this pathway is disrupted, porphyrin precursors accumulate. An accumulation of porphyrin precursors result in nervous system symptoms and when exposed to light, these porphyrin precursors cause the skin manifestations seen in porphyria. Porphyria primarily affects the skin, the nervous system and sometimes involves other organs such as the liver. Symptoms and signs of porphyria vary greatly amongst individuals and are often dependent on the type and cause of the condition in that individual. Each different type of porphyria is due to the abnormality of a different enzyme in the haem producing pathway.
Porphyrias are often categorized in the literature in two general categories. The category of hepatic porphyrias are porphyrias where the accumulation initially occurs in the liver and symptoms often manifest in adulthood. The category of erythropoietic porphyrias refers to when the accumulation initially occurs in the bone marrow and this results in symptoms much earlier in life. Furthermore, although there are a number of different porphyrias, porphyria is often classified clinically in three different types; however, they are not completely distinct and can overlap. Acute porphyria mainly affects the nervous system and symptoms can be varied and periodic but includes pain and weakness of the extremities, psychological changes in mood, gastrointestinal conditions and non-specific abdominal pain amongst other debilitating symptoms. The Cutaneous porphyrias refer to those with skin manifestations. Following exposure to sunlight, individuals will often experience pigment changes in exposed areas, blistering and scarring. There is also Non-blistering Cutaneous porphyria which result in symptoms of acute pain and mood changes following sunlight exposure but without the chronic skin changes seen in other cutaneous types.
What is the cause?
The majority of porphyrias are caused by different pathogenic variants (gene mutations) that impact and disrupt the haem enzyme pathway, however, these are not always inherited and can occur in an individual for the first time. Depending on the variant/s involved the inheritance pattern may be dominant, recessive or x-linked dominant however, some individuals with the variant/s may never develop symptoms. Additional genetic factors and environmental triggers often result in the manifestation and severity of the symptoms, particularly in the category of hepatic porphyrias. Some of these external triggers include the use of certain medications, stress, alcohol, smoking, hormonal fluctuation or changes, changes in diet as a result of dieting or fasting. Attacks develop over hours or days and can last for days or weeks.
Diagnosing a porphyria in an individual is often thought to be challenging as symptoms are periodic, can resemble many other conditions and because it is rare, clinical suspicion is often the first step needed. Once diagnosed, management is dependent on the specific type of porphyria and is focussed on treating the presenting symptoms, preventing recurrent attacks and any long-term complications.
Do you want to learn more?
Visit www.porphyria.org.uk for excellent additional learning resources. It is Global Porphyria Day on Wednesday the 19th of April 2023. The BPA and the global porphyria community will engage in sharing their stories of their porphyria. Wear something purple and use the hashtag #PurpleForPorphyria as this is a great way to engage in awareness. For further resources and information on how you can #daretothinkrare and get involved follow this link: https://www.gpac-porphyria.org/global-porphyria-day-2023
References:
Anderson KE, Bloomer JR, Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR, Desnick RJ. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005 Mar 15;142(6):439-50. doi: 10.7326/0003-4819-142-6-200503150-00010. Erratum In: Ann Intern Med. 2005 Aug 16;143(4):316. Citation on PubMed
Badminton MN, Elder GH. Molecular mechanisms of dominant expression in porphyria. J Inherit Metab Dis. 2005;28(3):277-86. doi: 10.1007/s10545-005-8050-3. Citation on PubMed
Chemmanur AT, Bonkovsky HL. Hepatic porphyrias: diagnosis and management. Clin Liver Dis. 2004 Nov;8(4):807-38, viii. doi: 10.1016/j.cld.2004.07.001. Citation on PubMed
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Nordmann Y, Puy H. Human hereditary hepatic porphyrias. Clin Chim Acta. 2002 Nov;325(1-2):17-37. doi: 10.1016/s0009-8981(02)00276-0. Citation on PubMed
Peters TJ, Sarkany R. Porphyria for the general physician. Clin Med (Lond). 2005 May-Jun;5(3):275-81. doi: 10.7861/clinmedicine.5-3-275. No abstract available. Citation on PubMed
Sarkany RP. Making sense of the porphyrias. Photodermatol Photoimmunol Photomed. 2008 Apr;24(2):102-8. doi: 10.1111/j.1600-0781.2008.00336.x. Citation on PubMed
Sassa S. The porphyrias. Photodermatol Photoimmunol Photomed. 2002 Apr;18(2):56-67. doi: 10.1034/j.1600-0781.2002.180202.x. No abstract available. Citation on PubMed
Whatley SD, Ducamp S, Gouya L, Grandchamp B, Beaumont C, Badminton MN, Elder GH, Holme SA, Anstey AV, Parker M, Corrigall AV, Meissner PN, Hift RJ, Marsden JT, Ma Y, Mieli-Vergani G, Deybach JC, Puy H. C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet. 2008 Sep;83(3):408-14. doi: 10.1016/j.ajhg.2008.08.003. Epub 2008 Sep 4. Citation on PubMed or Free article on PubMed CentralWebsite: https://rarediseases.org/rare-diseases/porphyria/
