Hereditary coproporphyria is passed on in an autosomal dominant manner. It is caused by a set of mutations of the CPOX gene which drastically downregulates the enzymatic activity of CPO. CPO is involved in porphyrin and heme biosynthesis [1] [2].

Hereditary coproporphyria can develop in an acute and a chronic form. In its acute manifestation, patients may suffer from persisting nausea, vomiting attacks, severe epigastric abdominal and back pain lasting for several days, constipation, obstipation, cortical blindness, hypertension, hyponatremia, tachycardia, reddish urine and discrete seizure episodes, which can also lead to depression. Psychological symptoms typically present concomitantly with abdominal symptoms. Patients can also exhibit motor neuropathies characteristic of Guillain-Barré syndrome. Diffuse pain in the upper body has also been reported. Hereditary coproporphyria is usually asymptomatic between acute attacks.

In its chronic form, hereditary coproporphyria patients typically develop a long-lasting cutaneous photosensitivity in sun-exposed body parts such as hands and face. These body parts typically show a very fragile skin, hyperpigmented scars and bullae [3].

The probability of prevalence of the pathogenic CPOX mutations is equal in both, men and women. However, acute attacks affect women more often, in particular between menarche and menopause (age- 16 to 45). Attacks before puberty are very rare [3].

• Weight Loss

  The inciting event was the use of Hydroxycut™, an over-the-counter supplement to promote weight loss that has been reported to cause oxidative liver injury in vulnerable populations. [ncbi.nlm.nih.gov]

  If weight loss is desired, it is advisable to consult a physician and a dietitian about an individualized diet with modest caloric restriction (ca. 10%), which will produce gradual weight loss without increasing the risk of an attack of porphyria. [porphyriafoundation.blogspot.com]

  Loss & Acute Porphyria A Combination of Triggers Basic Dietary Information Eating Behavior and Porphyria Nutritional Management of Acute Porphyria Attacks The Glucose Effect in Acute Porphyrias Member Stories Media Porphyria Television and Other Media [porphyriafoundation.com]

  If nobody can reach my practice in rural West Virginia because of the weather, I’m still busy reading or writing appeal letters for durable medical equipment supplies or calculating weight loss plans for patients. [aafp.org]

• Severe Pain

  HCP is termed as a hepatic porphyria, meaning that the porphyrin compounds accumulate in the liver During acute attacks (presentation of severe symptoms), the disorder is characterized by severe abdominal pain, constipation or diarrhea, and neurological [dovemed.com]

  My pain started quite young at around the age of nine. That was my first inpatient hospital stay. At the time; I was diagnosed with a very severe case of gastroenteritis. [nationalpainreport.com]

  For severe pain, opiates are safe--that is, non-porphyrogenic. Pethidine, morphine, or diamorphine can be given. Chlorpromazine may be helpful to promote relaxation and sleep. [the-medical-dictionary.com]

• Collapse

  Moreover, the T fold has helices on one side of the sheet, but these helices are in a long collapsed hairpin β-α-α-β motif, whereas the connectivity is completely different in CPO. [pnas.org]

• Abdominal Pain

  The proband, a 13-year-old girl, presented with an acute episode of abdominal pain precipitated by barbiturates given for epileptic seizures. [annals.org]

  Both are considered rare differential diagnosis for acute abdominal pain. Case report 17 year old boy of Algerian origin presented with long history of recurrent episodes of fever, abdominal pain since infancy. [ped-rheum.biomedcentral.com]

  A 23-year-old man with epilepsy and a past history of abdominal pain and ileus, developed hypertension and arm and bulbar weakness when valproic acid and carbamazepine were reinitiated. [ncbi.nlm.nih.gov]

• Vomiting

  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 [rarediseases.info.nih.gov]

  On review of 111 cases, 35 per cent presented in acute attack: 80 per cent had abdominal pain, 34 per cent vomiting, 29 per cent solar sensitivity, 23 per cent neurological involvement, 23 per cent psychiatric symptoms and 20 per cent severe constipation [ncbi.nlm.nih.gov]

  The abdominal pain is often associated with lumbago irradiating to the thighs, and with nausea, vomiting and constipation. [orpha.net]

• Constipation

  On review of 111 cases, 35 per cent presented in acute attack: 80 per cent had abdominal pain, 34 per cent vomiting, 29 per cent solar sensitivity, 23 per cent neurological involvement, 23 per cent psychiatric symptoms and 20 per cent severe constipation [ncbi.nlm.nih.gov]

  Acute attacks most often result in neurovisceral symptoms that may include abdominal pain, constipation, and weakness. Less commonly, skin changes may occur. [patientslikeme.com]

  In its acute manifestation, patients may suffer from persisting nausea, vomiting attacks, severe epigastric abdominal and back pain lasting for several days, constipation, obstipation, cortical blindness, hypertension, hyponatremia, tachycardia, reddish [symptoma.com]

  The abdominal pain is often associated with lumbago irradiating to the thighs, and with nausea, vomiting and constipation. [orpha.net]

• Nausea

  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 [rarediseases.info.nih.gov]

  Other symptoms included intermittent headache, fatigue, abdominal pain and nausea. Porphyrin studies were markedly raised, with features consistent with hereditary coproporphyria (HCP). [ncbi.nlm.nih.gov]

  In its acute manifestation, patients may suffer from persisting nausea, vomiting attacks, severe epigastric abdominal and back pain lasting for several days, constipation, obstipation, cortical blindness, hypertension, hyponatremia, tachycardia, reddish [symptoma.com]

• Diarrhea

  Symptoms include pain in the chest or abdomen, vomiting, and diarrhea or constipation. During an attack, symptoms can include muscle numbness, tingling, paralysis, cramping, and personality or mental changes. [icd9data.com]

  This includes the acute attacks of abdominal pain, nausea, vomiting, diarrhea, tachycardia, hypertension and seizures, as well as the cutaneous findings seen in porphyria cutanea tarda (PCT), namely increased skin fragility, bullous lesions after exposure [en.wikipedia.org]

  However, these acute attacks are variable and can include vomiting, diarrhea, constipation, urinary retention, acute episodes of neuropathic symptoms, psychiatric symptoms, seizures, respiratory paralysis, tachycardia, and hypertension. [mayomedicallaboratories.com]

  HCP is termed as a hepatic porphyria, meaning that the porphyrin compounds accumulate in the liver During acute attacks (presentation of severe symptoms), the disorder is characterized by severe abdominal pain, constipation or diarrhea, and neurological [dovemed.com]

  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. [ghr.nlm.nih.gov]

• Tachycardia

  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 [rarediseases.info.nih.gov]

  In its acute manifestation, patients may suffer from persisting nausea, vomiting attacks, severe epigastric abdominal and back pain lasting for several days, constipation, obstipation, cortical blindness, hypertension, hyponatremia, tachycardia, reddish [symptoma.com]

  Tachycardia and hyponatremia are common during attacks. In cases with cardiac arrhythmia and respiratory paralysis (rare), attacks can be fatal. [orpha.net]

• Hypertension

  A 23-year-old man with epilepsy and a past history of abdominal pain and ileus, developed hypertension and arm and bulbar weakness when valproic acid and carbamazepine were reinitiated. [ncbi.nlm.nih.gov]

  In its acute manifestation, patients may suffer from persisting nausea, vomiting attacks, severe epigastric abdominal and back pain lasting for several days, constipation, obstipation, cortical blindness, hypertension, hyponatremia, tachycardia, reddish [symptoma.com]

  After that, the main goal is to prevent further convulsions and manage hypertension and organ damage. Episode 12 - Painless Brief Plot Summary Jeff is admitted to the hospital after an attempt at suicide. [housediseases.com]

  This includes the acute attacks of abdominal pain, nausea, vomiting, diarrhea, tachycardia, hypertension and seizures, as well as the cutaneous findings seen in porphyria cutanea tarda (PCT), namely increased skin fragility, bullous lesions after exposure [en.wikipedia.org]

• Photosensitivity

  A 26-year-old woman developed photosensitivity and jaundice after starting on an oral contraceptive agent. She was found to have hereditary coproporphyria. [ncbi.nlm.nih.gov]

• Visual Hallucination

  Psychological symptoms are variable: irritability, emotionality, depression, considerable anxiety and, more rarely, auditory and visual hallucinations, disorientation, mental confusion. [orpha.net]

  He additionally described transient auditory and visual hallucinations. Urine porphobilinogen was increased, consistent with an acute attack of porphyria. Urine porphyrins were raised at 156 nmol/mmol creatinine (normal range 0–30). [journals.lww.com]

• Seizure

  The proband, a 13-year-old girl, presented with an acute episode of abdominal pain precipitated by barbiturates given for epileptic seizures. [annals.org]

  Seizures are common in acute exacerbations of hepatic porphyria, even though the etiology is not identified in most cases. We have reported a case of normeperidine-induced seizures in a patient with hereditary coproporphyria. [ncbi.nlm.nih.gov]

  Proper drug selection is most difficult when it comes to treatment of the seizures that can accompany HCP, as most anti-seizure medications can make the symptoms worse. [en.wikipedia.org]

  Seizures still occur, but some seizures are not as apparent. Look at this for a more detailed explanation. [housediseases.com]

• Peripheral Neuropathy

  Hereditary coproporphyria can cause both peripheral neuropathy and central nervous system abnormalities. [ncbi.nlm.nih.gov]

  Peripheral neuropathies are predominantly motor neuropathies and can mimic Guillain-Barré syndrome. The weakness usually starts in the lower limbs and ascends, but neuropathies occur in any nerve distribution. [emedicine.medscape.com]

  I have spleenomegaly, colitis, cirrhosis, NASH, seizure disorder, severe anxiety disorder, visceral and peripheral neuropathy, undiagnosed reduced eye site that I have an appointment with a neuroophthamologist on 11/1/2017, and almost all of my teeth [nationalpainreport.com]

  Pubmed: 6502649 Barohn RJ, Sanchez JA, Anderson KE: Acute peripheral neuropathy due to hereditary coproporphyria. Muscle Nerve. 1994 Jul;17(7):793-9. doi: 10.1002/mus.880170715. [smpdb.ca]

• Personality Change

  Symptoms are pain in gut, limbs, or torso; paralysis, vomiting, constipation, personality changes, paranoia. These symptoms can last for hours, days, or weeks. [myporphyria.com]

  Other symptoms include: Muscle pain Muscle weakness or paralysis Numbness or tingling Pain in the arms or legs Pain in the back Personality changes Attacks can sometimes be life-threatening, producing: Low blood pressure Severe electrolyte imbalances [medlineplus.gov]

• Red Urine

  His manifestations were composed of all classical symptoms of acute hepatic porphyrias i.e. convulsions, psychosis, hypertension and respiratory failure as well as dark red urine with positive Watson-Schwartz test. [ncbi.nlm.nih.gov]

  Red Chloroform & red butanol layers - Porphobilinogen is insoluble in both : -- Red urine layers -- Clear chloroform & clear butanol layers Neurological/Psychiatric Forms of Porphyria -Abdominal Pain -Chest Pain -Nausea -Confusion -Depression -Hallucinations [quizlet.com]

  Urine and plasma osmolalities were consistent with the syndrome of inappropriate antidiuretic hormone secretion, at 572 and 247 mmol/kg, respectively. He subsequently developed dark red urine, with dipstick testing showing ketones only. [journals.lww.com]

  Some signs and symptoms of an acute attack are: pain, red, burning or blistering skin, red urine, neurological changes, or psychological changes. Resources BOOKS Deats-O'Reilly, Diana. Porphyria: The Unknown Disease. [healthofchildren.com]

  Patients present with hemolysis leading to splenomegaly, also due to increased deposition in the red blood cells. Diagnosis: Uroporphyrin I and coproporphyrin I accumulate in the bone marrow, red blood cells, plasma, urine, and feces. [clinicaladvisor.com]

• Dark Urine

  The patient showed dark urine, complained of hair loss and took since 1994 a hormonal oral contraceptive. No photosensitivity was observed. [ncbi.nlm.nih.gov]

  In some forms of porphyria, accumulated heme precursors excreted in the urine may cause various changes in color, after exposure to sunlight, to a dark reddish or dark brown color. Even a purple hue or red urine may be seen. [house.wikia.com]

In the initial screening procedure, it is reasonable to probe 5-aminolevulinic acid and porphobilinogen urine levels, which are expected to be increased by at least a factor of three during attacks. Urine porphyrin concentrations are another viable cross-check. Importantly, urine porphyrin levels can reduce back to normal or remain mildly elevated between attacks [4] [5]. Slightly increased but constant urine coproporphyrin levels are nonspecific and thus insufficient to corroborate the diagnosis. Serum sodium concentration should be checked in patients during attacks, since hyponatremia a quite common symptom. It is hardly feasible and advisable to directly measure the enzymatic activity of CPO.

Hereditary coproporphyria diagnosis mainly relies on solid evidence of elevated concentrations of coproporphyrins in the feces after a positive initial screening. Fecal coproporphyrin III levels can be up to 200 times higher than normal in absolute terms [6]. A direct initial test of fecal coproporphyrin III levels without further backup tests lacks specificity and sensitivity. The ratio of fecal coproporphyrin III to coproporphyrin concentrations has been shown to be a suitable check to probe for hereditary coproporphyria in adults. A dominant contribution (60-95%) of the coproporphyrin III isomer in this ratio is characteristic of hereditary coproporphyria, while it is smaller than 50% in control groups [7] [8].

Abdominal pain symptoms in hereditary porphyria have been rationalized with elevated urine levels of the heme precursor molecule delta-aminolevulinic acid. Administration of hemin relieves pain symptoms during attacks because it inhibits the catalysis of delta-aminolevulinic acid by aminolevulinic acid synthase-1 [9].

• Hyponatremia

  Serum sodium concentration should be checked in patients during attacks, since hyponatremia a quite common symptom. It is hardly feasible and advisable to directly measure the enzymatic activity of CPO. [symptoma.com]

  Tachycardia and hyponatremia are common during attacks. In cases with cardiac arrhythmia and respiratory paralysis (rare), attacks can be fatal. [orpha.net]

  It is very important to monitor patients with hyponatremia because they can develop seizures. [hematologyandoncology.net]

  […] affected Anemia and related conditions, due to low levels of oxygen transport Increased heart rate and increased blood pressure may be the outcome of autonomic nervous system being affected If the neuroendocrine region of brain is affected, it can lead to hyponatremia [dovemed.com]

• Hepatocellular Carcinoma

  A 58-yr-old woman with hereditary coproporphyria presented with a 3.5-cm-diameter hepatocellular carcinoma. Results of exhaustive investigation of etiological factors for hepatocellular carcinoma were negative. [ncbi.nlm.nih.gov]

  Long-term risks for hypertension, impaired renal function. and hepatocellular carcinoma are increased. Low grade abnormalities in the liver function tests are common. The risk of hepatocellular carcinoma is increased. [clinicaladvisor.com]

  carcinoma/hepatoma 肝細胞癌 hepatocyte 肝細胞 hepatocyte growth factor 肝細胞増殖因子 HGF hepatoerythropoietic porphyria 肝造血性ポルフィリン症 hepatolenticular degeneration 肝レンズ核変性症/肝レンズ核変性 hepatomegaly 肝腫大 hepatoportoenterostomy 肝門部肝空腸吻合術/肝門部肝空腸吻合法 hepatorenal syndrome 肝腎症候群 [jpeds.or.jp]

  carcinoma 肝サルコイドーシス hepatic sarcoidosis 肝紫斑病 peliosis hepatis 肝ジストマ症 clonorchis sinensis, liver flukes, distomatosis hepatis, hepatodistomiasis 肝静脈閉塞 hepatic veno occlusive disease 肝性骨髄性ポルフィリン症 hepatoerythropoietic porphyria 肝腎型チロシン血症 hepatorenal tyrosinemia [jsge.or.jp]

We report a successful treatment with lamotrigine of a patient with hereditary coproporphyria presenting with affective and psychotic symptoms. [ncbi.nlm.nih.gov]

Treatment is based on preventing the symptoms. An acute attack requires hospitalization, medications, and treatment with heme therapy. [4] Last updated: 9/4/2019 [rarediseases.info.nih.gov]

What are treatments for Hereditary Coproporphyria? Treatment, complications, and preventive measures are the same as in AIP. Hospitalization is often necessary for acute attacks. [porphyriafoundation.blogspot.com]

What is the Prognosis of Hereditary Coproporphyria? (Outcomes/Resolutions) The prognosis of Hereditary Coproporphyria varies with the severity of the condition. [dovemed.com]

Prognosis With early diagnosis and management, attacks from porphyria are rarely fatal. Acute attacks are more rare than in cases of acute intermittent porphryia and, if the triggering factors are eliminated, the disease is rarely progressive. [orpha.net]

The prognosis is usually good if the disease is recognized and treated promptly, before nerve damage develops. [porphyriafoundation.blogspot.com]

H&O What is the prognosis for someone with acute porphyria? MB The overall prognosis is good because specific treatment is available, but symptoms must be recognized and managed correctly. [hematologyandoncology.net]

Results of exhaustive investigation of etiological factors for hepatocellular carcinoma were negative. Results of microscopic histological analysis of the nontumorous liver were normal. [ncbi.nlm.nih.gov]

Etiology Hereditary coproporphyria is caused by a deficiency of coproporphyrinogen oxidase (CPO, the sixth enzyme in the heme biosynthesis pathway) that leads to an accumulation of porphyrins and their precursors in the liver (delta-aminolevulinic acid [orpha.net]

Our findings add substantially to knowledge of the molecular epidemiology of HCP, show that single copies of CPO mutations that are known or predicted to cause "homozygous" HCP or harderoporphyria can produce typical HCP in adults, and demonstrate that [ncbi.nlm.nih.gov]

Summary Epidemiology The prevalence in Europe is estimated at about 1/1,000,000. Clinical description The disease manifests after puberty and preferentially affects women. [orpha.net]

Relevant External Links for CPOX Genetic Association Database (GAD) CPOX Human Genome Epidemiology (HuGE) Navigator CPOX Atlas of Genetics and Cytogenetics in Oncology and Haematology: CPOX No data available for Genatlas for CPOX Gene The association [genecards.org]

[…] neurovisceral attacks always have elevations of porphobilinogen and ALA, researchers still are unclear about how this leads to the symptomatic disease because most patients with the genetic defect have excessive porphyrin secretion but no symptoms. [1] Epidemiology [emedicine.com]

In an oral stomatology practice, a group of patients having oral conditions with unknown pathophysiology and multiple systemic complaints were evaluated for porphyrin abnormalities. Blood enzymes, urine and stool porphyrin panels were usually run. [ncbi.nlm.nih.gov]

Balances summaries of relevant pathophysiology with clear, practical clinical guidance to help you thoroughly understand the underlying science of diseases. [books.google.com]

The pathophysiology of both neurologic and psychiatric symptoms is not fully understood. [eurekaselect.com]

Pathophysiology Coproporphyria is an autosomal dominant disease that results from defects in the enzyme coproporphyrinogen oxidase. This enzyme speeds the conversion of coproporphyrinogen to protoporphyrinogen. [emedicine.com]

Very frequent premenstrual attacks can be prevented by a gonadotropin-releasing hormone (GnRH) analogue administered with expert guidance. In selected cases, frequent noncyclic attacks can be prevented by once- or twice-weekly infusions of hemin. [porphyriafoundation.blogspot.com]

Avoiding your triggers will help prevent bouts of symptoms. Remember that everyone with porphyria is different. Some people have milder symptoms than others. Treatments can help you feel better and prevent complications. [webmd.com]

Treatment is based on preventing the symptoms. An acute attack requires hospitalization, medications, and treatment with heme therapy. [4] Last updated: 9/4/2019 [rarediseases.info.nih.gov]

The identification of the genetic defect in HCP families is of crucial importance to detect the carrier status which allows counselling to prevent possible triggering factors, e.g. certain drugs, alcohol, or fasting. [ncbi.nlm.nih.gov]

1. Dong-Sun L, Flachsová E, Bodnárová M, Demeler B, Martásek P, Raman CS. Structural basis of hereditary coproporphyria. Proc Natl Acad Sci U S A. 2005;102(40):14232–14237.
2. Rosipal R, Lamoril J, Puy H, et al. Systematic analysis of coproporphyrinogen oxidase gene defects in hereditary coproporphyria and mutation update. Hum Mutat. 1999;13(1):44-53.
3. Bissell DM, Wang B, Lai J. Hereditary Coproporphyria. In: Pagon RA, Adam MP, Ardinger HH, et al. eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK114807/ Accessed March 27th 2017.
4. Roshal M, Turgeon J, Rainey PM. Rapid quantitative method using spin columns to measure porphobilinogen in urine. Clin Chem. 2008;54(2):429-431.
5. Stein P, Badminton M, Barth J, Rees D, Stewart MF. Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem. 2013;50(3):217-223.
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(7):1406-1414.
7. Kühnel A, Gross U, Doss MO. Hereditary coproporphyria in Germany: clinical-biochemical studies in 53 patients. Clin Biochem. 2000;33(6):465-473.
8. Blake D, McManus J, Cronin V, Ratnaike S. Fecal coproporphyrin isomers in hereditary coproporphyria. Clin Chem. 1992;38(1):96-100.
9. Bissell DM, Lai JC, Meister RK, Blanc PD. Role of delta-aminolevulinic acid in the symptoms of acute porphyria. Am J Med. 2015;128:313–317.