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Sunday, April 22, 2018
#PAW2018 Medical Moment What is HCP
What is Hereditary Coproporphyria?
HCP is due to a mutation in coproporphyinogen oxidase (CPOX), which is part of the pathway that produces porphyrins and heme. It is an autosomal dominant disorder, meaning that a mutation is present in only one of the pair of CPOX genes. The incidence of active HCP appears to be at most 2 per 1,000,000. The prevalence of the genetic carrier state is unknown.
Who gets Hereditary Coproporphyria?
HCP is termed a disease with low penetrance, meaning that many genetic carriers (defined by having a CPOX mutation) never have signs or symptoms of active porphyria. Active disease in general requires the presence of environmental factors such as certain drugs, hormones, and dietary changes, as in AIP. Lists are available of drugs that are risky for HCP genetic carriers as well as drugs that are safe (http://www.porphyriafoundation.com/testing-and-treatment/drug-safety-in-acute-porphyria). The worst offenders are barbiturates, sulfonamide antibiotics, anti-seizure drugs, rifampin, and oral contraceptives (progesterone, in particular). Attacks in women may occur after ovulation and during the last part of the menstrual cycle when progesterone levels are high. Reduced food intake, often in an effort to lose weight, as well as infections, surgery, and stressful situations may also precipitate attacks. Alcohol has been implicated in some attacks. People with repeated attacks are at risk for developing chronic renal disease and liver cancer (hepatocellular carcinoma)
How is Hereditary Coproporphyria diagnosed?
The initial test for people with symptoms is quantitative urinary aminolevulinic acid (ALA), porphobilinogen (PBG) and porphyrins. Elevation of ALA, PBG and coproporphyrin (predominantly isomer III) is highly suggestive of HCP. For asymptomatic individuals, the urine studies may be normal, but a fecal porphyrin analysis will show elevation of coproporphyrin III. Screening tests of this kind should be confirmed by DNA analysis to confirm a CPOX mutation.
What are treatments for Hereditary Coproporphyria?
Treatment, complications, and preventive measures are the same as in AIP. Hospitalization is often necessary for acute attacks. Medications for pain, nausea, and vomiting and close observation are generally required. During treatment of an attack, attention should be given to sodium (salt) and water balance. Harmful drugs should be stopped. Attacks are treated with either glucose loading or hemin (Panhematin®, Recordati). These are specific treatments that lower the production of heme pathway intermediates by the liver. Glucose or other carbohydrates are given by mouth if possible, otherwise by vein. However, unless an attack is mild, it is now common practice to give hemin as soon as it is available, because it works more quickly than glucose loading, preventing the neurological complications of prolonged attacks.
Patients with severe renal disease tolerate hemodialysis or kidney transplantation. Liver transplantation has been very effective for patients who have repeated attacks and who are resistant to other treatments. However, experience with transplantation as a treatment is still limited.
What is the long-term outlook after an attack of Hereditary Coproporphyria?
The prognosis is usually good if the disease is recognized and treated promptly, before nerve damage develops. Although symptoms usually resolve after an attack, recovery of neuromuscular function (in a severe case) may require several months or longer. Mental symptoms may occur during attacks but are not chronic. Premenstrual attacks often resolve quickly with the onset of menses.
Can attacks be prevented?
Yes, particularly with regard to drugs and diet. Genetic HCP carriers should become informed on drugs and other factors that can lead to symptoms (see above). They should be prepared to point their healthcare providers to drugs and medications to avoid. The American Porphyria Foundation offers a mobile phone app that pulls up this information on line (http://porphyriadrugs.com/). A Medic Alert bracelet is useful for a situation in which the patient is incapacitated. 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.
Individuals who are prone to attacks should consume a normal balanced diet. Despite on-line discussion, there is no evidence that pushing carbohydrate prevents attacks, and it has the side effect of weight gain, which is undesirable for most people. Fasting, fad diets (for example, high protein) and gastric reduction surgery should be avoided. 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. Exercise is safe in porphyria, and recommended.
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