Rare Rheumatology News

Disease Profile

Hereditary coproporphyria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adolescent

ICD-10

E80.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Coproporphyria; Coproporphyria hereditary; Hereditary coproporphyria porphyria;

Categories

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders;

Summary

Hereditary coproporphyria (HCP) is a rare inherited form of liver (hepatic) porphyria, characterized by neurological symptoms in the form of episodes (acute attacks) of stomach pain, nausea, vomiting, weakness, numbness, and pain in the hands and feet (neuropathy).[1][2] The porphyrias are a group of blood conditions caused by a lack of an enzyme in the body that makes heme, an important molecule that carries oxygen throughout the body and is vital for all of the body’s organs.[1] Symptoms usually begin around 20-30 years of age, but have been reported at younger ages. Signs and symptoms present during the attacks may include body pain, nausea and vomiting, increased heart rate (tachycardia), and high blood pressure.[2] Less common symptoms include seizures, skin lesions, and paralysis of the arms and legs, body trunk, and respiratory muscles. Most individuals with HCP do not have any signs or symptoms between attacks.[3] HCP is caused by mutations in the CPOX gene and is inherited in an autosomal dominant manner.[1268] Diagnosis is based on the symptoms and specific blood, urine and stool testing. Treatment is based on preventing the symptoms. An acute attack requires hospitalization, medications, and treatment with heme therapy.[4]

Symptoms

The symptoms of hereditary coproporphyria (HCP) may be different from person to person. Some people may be more severely affected than others and not everyone with hereditary coproporphyria will have the same symptoms. Many individuals with a CPOX gene mutation do not experience any symptoms of HCP.[3][5] 

In people with HCP, additional factors; such as hormonal changes, certain drugs, excess alcohol consumption, infections, and fasting or dietary changes; may trigger the appearance of symptoms. Symptoms appear as acute attacks or episodes that develop over a period of days. The timing and severity of attacks vary from one person to another.[1]

The symptoms of an acute attack include:[2]

Severe stomach pain leading to nausea and vomiting
-back and leg pain
High blood pressure
Rapid heartbeat (tachycardia)
Seizures (less common)
Weakness, numbness in the arms and legs (peripheral neuropathy)
Skin findings (in about 20% of people with HCP)
-extreme sensitivity to sunlight (photosensitivity)
-fragile skin

In between attacks, people with HCP are often symptom-free. 

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abdominal pain
Stomach pain
Pain in stomach

[ more ]

0002027
Abnormal circulating porphyrin concentration
0010472
Elevated urinary delta-aminolevulinic acid
0003163
30%-79% of people have these symptoms
Atypical scarring of skin
Atypical scarring
0000987
Dark urine
0040319
Distal muscle weakness
Weakness of outermost muscles
0002460
Episodic vomiting
0002572
Increased urinary porphobilinogen
0012217
Limb pain
0009763
Nausea
0002018
Porphyrinuria
0010473
Proximal muscle weakness in lower limbs
0008994
Proximal muscle weakness in upper limbs
0008997
5%-29% of people have these symptoms
Abnormal blistering of the skin
Blistering, generalized
Blisters

[ more ]

0008066
Back pain
0003418
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity

[ more ]

0000992
Extension of hair growth on temples to lateral eyebrow
0005325
Facial hirsutism
0009937
Fragile skin
Skin fragility
0001030
Hepatocellular carcinoma
0001402
Hyponatremia
Low blood sodium levels
0002902
Long hairs growing from helix of pinna
Long hairs growing from helix of ear
0008528
Motor polyneuropathy
0007178
Nephropathy
0000112
Psychosis
0000709
Respiratory insufficiency
Respiratory impairment
0002093
Seizure
0001250
Small intestinal dysmotility
0012850
Tachycardia
Fast heart rate
Heart racing
Racing heart

[ more ]

0001649
1%-4% of people have these symptoms
Acute episodes of neuropathic symptoms
0003489
Increased fecal coproporphyrin 3
0033010
Percent of people who have these symptoms is not available through HPO
Anxiety
Excessive, persistent worry and fear
0000739
Autosomal dominant inheritance
0000006
Confusion
Disorientation
Easily confused
Mental disorientation

[ more ]

0001289
Constipation
0002019
Depressivity
Depression
0000716
Diarrhea
Watery stool
0002014
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hepatomegaly
Enlarged liver
0002240
Hypertension
0000822
Incomplete penetrance
0003829
Insomnia
Difficulty staying or falling asleep
0100785
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Paranoia
0011999
Peripheral neuropathy
0009830
Respiratory paralysis
0002203
Splenomegaly
Increased spleen size
0001744
Vomiting
Throwing up
0002013
Young adult onset
0011462

Cause

Hereditary coproporphyria (HCP) is caused by a genetic change (mutation in the CPOX gene. However, having a CPOX gene mutation alone does not cause symptoms. Additional factors (such as hormonal changes, specific drugs, excess alcohol, fasting) are needed to trigger an attack and the appearance of symptoms. Some people with CPOX gene mutations never have symptoms of HCP.[2]

The American Porphyria Foundation offers a drug database with safety information about the interaction of specific drugs in patients with porphyria. 

Diagnosis

The diagnosis of hereditary coproporphyria (HCP) is suspected first based on the clinical signs and symptoms, usually during an acute attack. Once a person is suspected of having HCP, examination of urine, blood, and stool (fecal) samples is typically done. These lab tests are usually done at the time of the acute attack and look for elevated levels of compounds found to be associated with several different types of porphyria.[2][5]

To identify the specific type of porphyria an individual has, genetic testing can be performed to look for mutations in the CPOX gene.[2]

At least one study suggesting diagnostic criteria for the acute dominantly inherited forms of porphyria has been published.[6]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is no specific treatment for hereditary coproporphyria (HCP). Treatment is aimed at managing the symptoms of HCP that occur during an acute attack. Hospitalization is often necessary for acute attacks, and medications for pain, nausea and vomiting, and close observation are generally required. Some attacks may be managed by giving the person a large amount of glucose or other carbohydrates. More severe attacks are treated with heme therapy, given through a vein (intravenously). Panhematin® is currently the only commercially available heme therapy for treatment and prevention of acute porphyria attacks in the United States. Heme arginate, which is marketed in some other countries, is another type of heme therapy.[1][2][4]

    Attacks can also be avoided by avoiding the ‘trigger’ for the attack. The trigger can be different for different people. Triggers include certain medications, alcohol, dieting, and hormonal changes in the body. Sometimes, however, the trigger is unknown. If the person with HCP has skin symptoms, avoiding excess sun exposure can reduce the blisters and skin lesions.[4][5]

    Management Guidelines

    • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.
    • The American Porphyria Foundation offers a document that includes information about porphyria, types, testing, and treatment with Panhematin®. Click the "document" link above to view these guidelines.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Social Networking Websites

        • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

          Organizations Providing General Support

            Learn more

            These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

            Where to Start

            • The The American Porphyria Foundation offers an information page on Hereditary coproporphyria. Please click on the link to access this resource.
            • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
            • Genetics Home Reference (GHR) contains information on Hereditary coproporphyria. This website is maintained by the National Library of Medicine.
            • The National Digestive Diseases Information Clearinghouse (NIDDK) offers information on this condition. Click on the link to view information on this topic.
            • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
            • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

              In-Depth Information

              • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
              • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
              • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
              • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
              • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
              • PubMed is a searchable database of medical literature and lists journal articles that discuss Hereditary coproporphyria. Click on the link to view a sample search on this topic.

                References

                1. Tishler, Peter. Hereditary Coproporphyria. National Organization for Rare Disorders (NORD). Updated 2014; https://rarediseases.org/rare-diseases/hereditary-coproporphyria/.
                2. Wang B, Bissell, DM. Hereditary Coproporphyria. GeneReviews. Updated Nov. 8, 2018; https://www.ncbi.nlm.nih.gov/books/NBK114807/.
                3. Wang B, Rudnick S, Cengia B, Bonkovsky HL. Acute hepatic porphyrias: Review and recent progress. Hepato Comm. Dec 20, 2018; 3(2):193-206. https://www.ncbi.nlm.nih.gov/pubmed/30766957.
                4. Balwani M, Wang B, Anderson KE, Bloomer JR, Bissell DM, Bonkovsky HL, Phillips JD, Desnick RJ, et al.. Acute hepatic porphyrias: recommendations for evaluation and long-term management. Hepatology. 2017; 66:1314-1322. https://www.ncbi.nlm.nih.gov/pubmed/28605040.
                5. Stein PE, Badminton MN, Rees DC.. Update review of the acute porphyrias. Br Jl Hemot. 2017; 176(4):527-538. https://www.ncbi.nlm.nih.gov/pubmed/27982422.
                6. Whatley SD, Mason NG, Woolf JR, Newcombe RG, Elder GH, Badminton MN. Diagnostic strategies for autosomal dominant acute porphyrias: retrospective analysis of 467 unrelated patients referred for mutational analysis of the HMBS, CPOX, or PPOX gene. Clin Chem. 2009; 55:1406-1414. https://www.ncbi.nlm.nih.gov/pubmed/19460837.
                7. Elder G1, Harper P, Badminton M, Sandberg S, Deybach JC. The incidence of inherited porphyrias in Europe. J Inherit Metab Dis. Sep 2013; 36(5):849-57. https://www.ncbi.nlm.nih.gov/pubmed/23114748.

                Rare Rheumatology News