Porphyria, Acute Intermittent
Porphyria Cutanea Tarda
Mutations in human CPO gene predict clinical expression of either hepatic hereditary coproporphyria or erythropoietic harderoporphyria. (1/6)Hereditary coproporphyria (HCP), an autosomal dominant acute hepatic porphyria, results from mutations in the gene that encodes coproporphyrinogen III oxidase (CPO). HCP (heterozygous or rarely homozygous) patients present with an acute neurovisceral crisis, sometimes associated with skin lesions. Four patients (two families) have been reported with a clinically distinct variant form of HCP. In such patients, the presence of a specific mutation (K404E) on both alleles or associated with a null allele, produces a unifying syndrome in which hematological disorders predominate: 'harderoporphyria'. Here, we report the fifth case (from a third family) with harderoporphyria. In addition, we show that harderoporphyric patients exhibit iron overload secondary to dyserythropoiesis. To investigate the molecular basis of this peculiar phenotype, we first studied the secondary structure of the human CPO by a predictive method, the hydrophobic cluster analysis (HCA) which allowed us to focus on a region of the enzyme. We then expressed mutant enzymes for each amino acid of the region of interest, as well as all missense mutations reported so far in HCP patients and evaluated the amount of harderoporphyrin in each mutant. Our results strongly suggest that only a few missense mutations, restricted to five amino acids encoded by exon 6, may accumulate significant amounts of harderoporphyrin: D400-K404. Moreover, all other type of mutations or missense mutations mapped elsewhere throughout the CPO gene, lead to coproporphyrin accumulation and subsequently typical HCP. Our findings, reinforced by recent crystallographic results of yeast CPO, shed new light on the genetic predisposition to HCP. It represents a first monogenic metabolic disorder where clinical expression of overt disease is dependent upon the location and type of mutation, resulting either in acute hepatic or in erythropoietic porphyria. (+info)
Structural basis of hereditary coproporphyria. (2/6)Hereditary coproporphyria is an autosomal dominant disorder resulting from the half-normal activity of coproporphyrinogen oxidase (CPO), a mitochondrial enzyme catalyzing the antepenultimate step in heme biosynthesis. The mechanism by which CPO catalyzes oxidative decarboxylation, in an extraordinary metal- and cofactor-independent manner, is poorly understood. Here, we report the crystal structure of human CPO at 1.58-A resolution. The structure reveals a previously uncharacterized tertiary topology comprising an unusually flat seven-stranded beta-sheet sandwiched by alpha-helices. In the biologically active dimer (K(D) = 5 x 10(-7) M), one monomer rotates relative to the second by approximately 40 degrees to create an intersubunit interface in close proximity to two independent enzymatic sites. The unexpected finding of citrate at the active site allows us to assign Ser-244, His-258, Asn-260, Arg-262, Asp-282, and Arg-332 as residues mediating substrate recognition and decarboxylation. We favor a mechanism in which oxygen serves as the immediate electron acceptor, and a substrate radical or a carbanion with substantial radical character participates in catalysis. Although several mutations in the CPO gene have been described, the molecular basis for how these alterations diminish enzyme activity is unknown. We show that deletion of residues (392-418) encoded by exon six disrupts dimerization. Conversely, harderoporphyria-causing K404E mutation precludes a type I beta-turn from retaining the substrate for the second decarboxylation cycle. Together, these findings resolve several questions regarding CPO catalysis and provide insights into hereditary coproporphyria. (+info)
Neurovisceral porphyrias: what a hematologist needs to know. (3/6)The acute or inducible hepatic porphyrias comprise four inherited disorders of heme biosynthesis. They usually remain asymptomatic for most of the lifespan of individuals who inherit the specific enzyme deficiencies but may cause life-threatening attacks of neurovisceral symptoms. Failure to consider the diagnosis frequently delays effective treatment, and inappropriate diagnostic tests and/or mistaken interpretation of results may lead to misdiagnosis and inappropriate treatment. The four disorders are ALA dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Other conditions that clinically and biochemically may mimic acute porphyria include lead poisoning and hereditary tyrosinemia type I. The diagnosis of one of these acute porphyric syndromes should be considered in many patients with otherwise unexplained abdominal pain, severe constipation, systemic arterial hypertension, or other characteristic symptoms. Critical to the rapid diagnosis of the three most common of these disorders is demonstration of markedly increased urinary porphobilinogen (PBG) in a single-void urine specimen. The treatment of choice for all but mild attacks of the acute porphyrias is intravenous hemin therapy, which should be started as soon as possible. Intravenous glucose alone is recommended only for mild attacks (no weakness or hyponatremia) or until hemin is available. (+info)
Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R. (4/6)(+info)
Digenic inheritance of mutations in the coproporphyrinogen oxidase and protoporphyrinogen oxidase genes in a unique type of porphyria. (5/6)(+info)
Lamotrigine in the treatment of psychotic depression associated with hereditary coproporphyria -- case report and a brief review of the literature. (6/6)OBJECTIVE: We report a successful treatment with lamotrigine of a patient with hereditary coproporphyria presenting with affective and psychotic symptoms. CASE REPORT: M.F., a 38-year-old, single woman was admitted to an acute psychiatric ward because of suddenly emerging psychosis. Ms F's hereditary coproporphyria was diagnosed 9 years before the current admission. While on treatment with olanzapine (20mg/day) the psychotic symptoms have gradually disappeared. In view of her significant mood fluctuations predominantly with depressed phases, lamotrigine was started and titrated up to 125 mg/day. Ms F's mood gradually became euthymic, suicidal ideations and anxiety disappeared. At 5-month follow-up, while still on lamotrigine, her porphyria was asymptomatic. CONCLUSION: To the best of our knowledge, this is the first report about the safe administration of lamotrigine in hereditary coproporphyria. Lamotrigine did not trigger an acute porphyric attack as confirmed by clinical and laboratory findings. (+info)
There are several types of coproporphyria, including:
1. Coproporphyria type I (CP I): This is the most common form of the disorder and is caused by mutations in the CPOX gene. Symptoms typically appear during infancy or childhood and can include seizures, developmental delays, and liver problems.
2. Coproporphyria type II (CP II): This form of the disorder is caused by mutations in the FECH gene and typically affects adults. Symptoms can include neurological problems, such as seizures and nerve damage, as well as liver dysfunction.
3. Coproporphyria type III (CP III): This rare form of the disorder is caused by mutations in the PPOX gene and typically affects children. Symptoms can include seizures, developmental delays, and liver problems.
4. Hereditary coproporphyria (HCP): This is a milder form of the disorder that is caused by mutations in the CPOX or FECH gene. Symptoms can include neurological problems, such as seizures and nerve damage, as well as liver dysfunction.
There is no cure for coproporphyria, but treatment options are available to manage symptoms and prevent complications. These can include medications to reduce seizures and inflammation, as well as dietary changes and liver transplantation in severe cases. Early diagnosis and management of the disorder can help improve quality of life for individuals affected by coproporphyria.
Note: Porphyria is a medical emergency and requires immediate attention if symptoms persist or worsen over time.
There are several types of porphyria, each with different symptoms and characteristics. Some of the most common types include:
1. Acute intermittent porphyria (AIP): This is the most common form of porphyria, and it is characterized by sudden episodes of severe abdominal pain, nausea, vomiting, and constipation. These episodes can be triggered by factors such as alcohol, certain medications, and hormonal changes.
2. Hereditary coproporphyria (HCP): This type of porphyria is caused by a deficiency of the enzyme coproporphyrinogen oxidase, which is needed to produce heme. Symptoms of HCP include abdominal pain, nausea, vomiting, and constipation, as well as neurological symptoms such as seizures, confusion, and memory loss.
3. Porphyria cutanea tarda (PCT): This type of porphyria is characterized by skin symptoms, including blistering, itching, and sensitivity to sunlight. PCT can also cause liver damage and an increased risk of skin cancer.
4. Congenital erythropoietic porphyria (CEP): This is a rare and severe form of porphyria that is present at birth. CEP is characterized by anemia, enlarged liver and spleen, and a high risk of infection.
There is no cure for porphyria, but treatment options are available to manage symptoms and prevent complications. These may include avoiding triggers such as alcohol and certain medications, taking medications to relieve symptoms, and receiving regular monitoring and supportive care. In some cases, a liver transplant may be necessary.
Porphyria is a complex and rare group of disorders that can have a significant impact on quality of life. With proper diagnosis and management, however, it is possible for individuals with porphyria to lead full and active lives.
The symptoms of AI porphyria are caused by the buildup of toxic substances in the body, particularly in the nervous system and the gastrointestinal tract. These symptoms can be triggered by factors such as alcohol consumption, fasting, and certain medications.
There is no cure for AI porphyria, but treatment options are available to manage symptoms and prevent complications. These may include medications to reduce nausea and vomiting, anticonvulsants to prevent seizures, and blood transfusions to increase hemoglobin levels. In severe cases, a liver transplant may be necessary.
Preventative measures for AI porphyria include avoiding triggers such as alcohol and fasting, taking medications as prescribed by a healthcare provider, and maintaining a consistent diet. Regular monitoring and follow-up with a healthcare provider are also important to manage the condition effectively.
Slide 2: Symptoms of Porphyria, Erythropoietic
Symptoms of porphyria, erythropoietic can vary in severity and may include:
1. Anemia: A low red blood cell count can lead to fatigue, weakness, and shortness of breath.
2. Weakness and abdominal pain: Porphyrins can accumulate in the abdomen and cause pain and discomfort.
3. Pale skin and mucous membranes: A lack of red blood cells can lead to pale skin and mucous membranes.
4. Nausea and vomiting: Porphyrins can cause nausea and vomiting.
5. Increased risk of infection: Porphyria, erythropoietic can increase the risk of infection due to a weakened immune system.
6. Kidney damage: Prolonged exposure to porphyrins can damage the kidneys and lead to chronic kidney disease.
7. Seizures and mental changes: In severe cases, porphyria, erythropoietic can cause seizures and mental changes such as confusion and disorientation.
Slide 3: Causes and Diagnosis of Porphyria, Erythropoietic
1. Mutations in the UMOD gene: The UMOD gene provides instructions for making a protein called uromodulin, which is produced in the kidneys and plays a role in regulating the production of red blood cells. Mutations in this gene can lead to the development of porphyria, erythropoietic.
2. Familial history: There is a strong familial component to porphyria, erythropoietic, and individuals with a family history of the condition are more likely to develop it.
1. Physical examination: A physical examination may reveal signs such as abdominal pain, nausea and vomiting, and pale skin and mucous membranes.
2. Blood tests: Blood tests can be used to measure the levels of porphyrins in the blood and to diagnose the condition.
3. Urine tests: Urine tests may also be used to diagnose the condition and to rule out other conditions that may cause similar symptoms.
4. Genetic testing: Genetic testing may be used to identify mutations in the UMOD gene that are associated with porphyria, erythropoietic.
Slide 4: Treatment and Management of Porphyria, Erythropoietic
Treatment and management of porphyria, erythropoietic, typically involve a combination of medications, dietary changes, and avoiding triggers that can exacerbate the condition. The goal of treatment is to manage symptoms, prevent complications, and improve quality of life.
Treatment options may include:
1. Medications: Medications such as hydrochloroquine and chloroquine may be used to reduce the production of porphyrins in the body.
2. Dietary changes: Avoiding certain foods that are high in porphyrins, such as liver and other organ meats, can help reduce the symptoms of the condition.
3. Phototherapy: Exposure to specific wavelengths of light can help reduce the production of porphyrins in the body.
4. Blood transfusions: In severe cases of porphyria, erythropoietic, blood transfusions may be necessary to increase the levels of normal red blood cells in the body.
5. Liver transplantation: In some cases, liver transplantation may be necessary to treat the condition.
Slide 5: Prognosis and Quality of Life
The prognosis for patients with porphyria, erythropoietic, is generally good if the condition is properly managed. With appropriate treatment, most patients can lead a normal life expectancy and have a good quality of life. However, some patients may experience recurrent episodes of symptoms, which can impact their quality of life.
It is important for patients with porphyria, erythropoietic, to work closely with their healthcare provider to manage their condition and prevent complications. Patients should also be aware of the signs and symptoms of the condition and seek medical attention if they experience any new or worsening symptoms.
Slide 6: Prevention
Preventing porphyria, erythropoietic, is challenging, as it is a genetic condition that cannot be cured. However, there are some steps that can be taken to reduce the risk of developing the condition or exacerbating symptoms. These include:
1. Avoiding triggers: Patients should avoid triggers that can exacerbate the condition, such as certain medications, alcohol, and smoking.
2. Maintaining a healthy diet: Eating a balanced diet that is rich in fruits, vegetables, and whole grains can help to prevent nutritional deficiencies and reduce symptoms.
3. Getting regular exercise: Regular exercise can help to improve overall health and reduce the risk of complications.
4. Managing stress: Stress can exacerbate symptoms of porphyria, erythropoietic, so it is important for patients to find ways to manage stress, such as through relaxation techniques or therapy.
5. Avoiding exposure to certain chemicals: Patients should avoid exposure to certain chemicals that can trigger the condition, such as lead and other heavy metals.
Slide 7: Current Research
Research into porphyria, erythropoietic, is ongoing, and there are several current research studies focused on improving the diagnosis and treatment of the condition. Some of these studies include:
1. Investigating new treatments: Researchers are exploring new treatments for porphyria, erythropoietic, including gene therapy and other innovative approaches.
2. Improving diagnostic testing: Researchers are working to develop more accurate and reliable diagnostic tests for the condition, which could help to improve early detection and treatment.
3. Understanding the genetics of the condition: Scientists are studying the genetic factors that contribute to the development of porphyria, erythropoietic, in order to better understand the underlying causes of the condition.
4. Investigating the role of environmental triggers: Researchers are exploring the role of environmental triggers, such as exposure to certain chemicals, in the development of porphyria, erythropoietic.
Slide 8: Future Outlook
The future outlook for patients with porphyria, erythropoietic, is generally good if the condition is properly managed and treated. With ongoing research and advances in medical technology, there is hope for improving diagnostic testing and developing new and more effective treatments for the condition. Some of the potential future developments that could improve the outlook for patients with porphyria, erythropoietic, include:
1. New treatments: Researchers are exploring new treatments for porphyria, erythropoietic, such as gene therapy and stem cell transplantation.
2. Improved diagnostic testing: As diagnostic testing improves, it is likely that more patients will be diagnosed with the condition earlier in life, which could lead to better outcomes.
3. Increased awareness: Greater awareness of porphyria, erythropoietic, among healthcare professionals and the general public could help to improve early detection and treatment of the condition.
Slide 9: Conclusion
Porphyria, erythropoietic, is a rare genetic disorder that affects the production of heme, a vital component of hemoglobin. While there is currently no cure for the condition, ongoing research is exploring new treatments and diagnostic tools to improve outcomes for patients. With increased awareness and advances in medical technology, it is hopeful that the future outlook for patients with porphyria, erythropoietic, will continue to improve.
Slide 10: References
* National Organization for Rare Disorders (NORD). (2022). Porphyria, Erythropoietic. Retrieved from
* Genetic and Rare Diseases Information Center (GARD). (2022). Porphyria, Erythropoietic. Retrieved from
* American Porphyria Foundation. (2022). Erythropoietic Porphyria. Retrieved from
PCT typically affects adults in their 40s and 50s, with a slight predominance in males. The main symptoms include:
* Skin manifestations: PCT is characterized by blistering and scarring on sun-exposed areas, such as the face, hands, and arms. The skin lesions are usually painful and may be accompanied by itching.
* Nervous system manifestations: Some individuals with PCT may experience neurological symptoms, such as seizures, paralysis, and cognitive impairment.
* Increased risk of liver damage: PCT is associated with an increased risk of developing liver cancer and cirrhosis.
* Increased risk of cancer: Individuals with PCT have an increased risk of developing other types of cancer, such as lung, throat, and bladder cancer.
PCT is diagnosed based on a combination of clinical symptoms, laboratory tests, and genetic analysis. Treatment options for PCT include:
* Avoiding triggers such as sun exposure and certain medications
* Using protective clothing and sunscreen
* Medications to manage symptoms such as pain and itching
* Liver transplantation in advanced cases of liver damage
There is no cure for PCT, but early diagnosis and management can help reduce the severity of symptoms and improve quality of life.
Coproporphyrinogen III oxidase
The Home Depot
Aminolevulinic acid dehydratase deficiency porphyria
Polymorphous light eruption
Acute intermittent porphyria
Alcohol and cancer
List of MeSH codes (C06)
Syndrome of inappropriate antidiuretic hormone secretion
List of MeSH codes (C18)
List of MeSH codes (C16)
List of diseases (H)
List of diseases (P)
List of MeSH codes (C17)
List of OMIM disorder codes
List of skin conditions
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- Two porphyrias overlap these categories and can cause both neurovisceral and cutaneous symptoms, namely hereditary coproporphyria (HCP) and variegate porphyria (VP). (medscape.com)
- Acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and the familial form of porphyria cutanea tarda (PCT) follow an autosomal dominant inheritance pattern with low penetration. (medscape.com)
- This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT). (bvsalud.org)
- Chronic porphyrias include congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), hereditary coproporphyria (HCP) variegate porphyria (VP), erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP). (preventiongenetics.com)
- There are currently six different forms of chronic/cutaneous porphyria caused by specific pathogenic variants in genes involved in heme biosynthesis: hereditary coproporphyria ( CPOX ), variegate porphyria ( PPOX ), porphyria cutanea tarda/hepatoerythropoietic porphyria ( UROD ), congenital erythropoietic protoporphyria ( UROS ), erythropoietic protoporphyria ( FECH ), and X-linked protoporphyria ( ALAS2 ). (preventiongenetics.com)
- Hereditary coproporphyria and variegate porphyria only. (porphyria.ca)
- for vesiculobullous formation (suggesting porphyria cutanea tarda, hereditary coproporphyria, or variegate porphyria) a screening test for urinary porphyrins should be done. (qxmd.com)
- Hereditary coproporphyria (HCP) is an acute (hepatic) porphyria in which the acute symptoms are neurovisceral and occur in discrete episodes. (nih.gov)
- 13. [Acute liver porphyria--hereditary coproporphyria diagnosed for the first time in Czechoslovakia]. (nih.gov)
Involved in heme1
- Porphyria is the common term for a group of syndromes, largely hereditary, that result from defects in porphyrins (the enzymes involved in heme synthesis). (medscape.com)
- Defects in this gene are a cause of hereditary coproporphyria (HCP). (nih.gov)