Hereditary coproporphyria
Encyclopedia
Hereditary coproporphyria (HCP) is a type of acute porphyria
(formerly categorized as a form of hepatic porphyria
) that is associated with a deficiency of the enzyme coproporphyrinogen III oxidase
.
Hereditary coproporphyria (HCP) is an autosomal dominant genetic disease that causes purple urine
, photosensitivity
, and attacks of abdominal pain
. Symptoms vary from mild to severe and can be regulated with diet and triggered with drug use.
It has a prevalence
estimated at approximately 1 in 500,000.
Around 30% suffer photosensitive skin eruptions with nail involvement; these can lead to permanent scarring.
Attacks of coproporphyria can be life-threatening and should be dealt with accordingly. Treatment is the same as for acute Intermittent and variegate porphyria.
See Wikipedia article porphyria
for detailed information.
Triggers vary, but infections, hormonal changes
, dieting
, and the use of alcohol
and certain drugs such as barbiturates and hormonal contraceptives
have all been implicated.
s, or non-sex chromosomes. There have been documented cases of both heterozygous and homozygous inheritance, with similar symptoms in each patient.
(Dianabol). For more complete listings of drugs that may induce acute attacks, there are a number of online resources that may be referenced. These include NAPOS (the Norwegian Porphyria Centre), Porphyria South Africa, and http://www.porphyriafoundation.com/drug-database. All three databases have drugs listed in English. The Norwegian Porphyria Centre's list is also available in French and Swedish.
in the coproporphinogen oxidase (CPO) gene. Documented changes in the DNA
sequence that cause HCP include missense
, nonsense
, deletion
and splicing
of single nucleotides. Documented changes in the protein sequence have been a replacement of ser208 to phe(s208f) and arg328 to cys(r328c). Aside from varying intensity of symptoms there are no other known mutations, and it is not known at this time if mutations in other genes can trigger this same disease. At this time it is not known if there are any specific groups of people that are especially susceptible to this disease, as patients have been documented all over the world.
s, and 7 exon
s. Once the introns are spliced out the actual coded mRNA is only 2675 bases in length. The protein contains 323 amino acid
s.
is made from porphyrin and when a mutation occurs, heme production is interrupted. This leads to an overabundance of porphyrin in the body, which then exits through urine/feces.
Porphyria
Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway . They are broadly classified as acute porphyrias and cutaneous porphyrias, based on the site of the overproduction and accumulation of the porphyrins...
(formerly categorized as a form of hepatic porphyria
Hepatic porphyria
Hepatic porphyrias is a form of porphyria in which the enzyme deficiency occurs in the liver.Examples include :* Acute intermittent porphyria* Porphyria cutanea tarda and Hepatoerythropoietic porphyria...
) that is associated with a deficiency of the enzyme coproporphyrinogen III oxidase
Coproporphyrinogen III oxidase
Coproporphyrinogen-III oxidase, mitochondrial is an enzyme that in humans is encoded by the CPOX gene. A genetic defect in the enzyme results in a reduced production of heme in animals. The medical condition associated with this enzyme defect is called hereditary coproporphyria...
.
Hereditary coproporphyria (HCP) is an autosomal dominant genetic disease that causes purple urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, photosensitivity
Photosensitivity
Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light.- Human medicine :Sensitivity of the skin to a light source can take various forms. People with particular skin types are more sensitive to sunburn...
, and attacks of abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
. Symptoms vary from mild to severe and can be regulated with diet and triggered with drug use.
It has a prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
estimated at approximately 1 in 500,000.
Signs and symptoms
Signs and symptoms of an acute attack involve neurological dysfunction. Areas affected include the gastrointestinal tract resulting in extreme abdominal pain, vomiting, and constipation. Neurological dysfunction can be seen in the cardiovascular system as tachycardia and hypertension. There may also be pain in the extremities, muscle weakness, and sensory loss. Some may have psychological symptoms ranging from agitation to hallucinations. Urine may immediately have a reddish, brownish or purple coloring. However, others may not show this color change unless the urine is exposed to light for 30 minutes.Around 30% suffer photosensitive skin eruptions with nail involvement; these can lead to permanent scarring.
Attacks of coproporphyria can be life-threatening and should be dealt with accordingly. Treatment is the same as for acute Intermittent and variegate porphyria.
See Wikipedia article porphyria
Porphyria
Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway . They are broadly classified as acute porphyrias and cutaneous porphyrias, based on the site of the overproduction and accumulation of the porphyrins...
for detailed information.
Triggers vary, but infections, hormonal changes
Menstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....
, dieting
Dieting
Dieting is the practice of eating food in a regulated fashion to achieve or maintain a controlled weight. In most cases dieting is used in combination with physical exercise to lose weight in those who are overweight or obese. Some athletes, however, follow a diet to gain weight...
, and the use of alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
and certain drugs such as barbiturates and hormonal contraceptives
Hormonal contraception
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
have all been implicated.
Cause
HCP is an autosomal disease, meaning it is carried in one of the autosomeAutosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
s, or non-sex chromosomes. There have been documented cases of both heterozygous and homozygous inheritance, with similar symptoms in each patient.
Triggers of acute attacks
Acute attacks of porphyria can be induced by many drugs. The types of drugs may include but are not limited to progesterone, sulfonamides, anti-convulsants, steroids, and barbiturates. Cases noted hereditary coproporphyria induced by methandrostenoloneMethandrostenolone
Methandrostenolone is an orally-effective anabolic steroid originally developed by John Ziegler and released in the US in the early 1960s by Ciba. It was used as an aid to muscle growth by bodybuilders until its ban by Congress under the Controlled Substances Act...
(Dianabol). For more complete listings of drugs that may induce acute attacks, there are a number of online resources that may be referenced. These include NAPOS (the Norwegian Porphyria Centre), Porphyria South Africa, and http://www.porphyriafoundation.com/drug-database. All three databases have drugs listed in English. The Norwegian Porphyria Centre's list is also available in French and Swedish.
Pathophysiology
Hereditary coproporphyria is the result of a point mutationPoint mutation
A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...
in the coproporphinogen oxidase (CPO) gene. Documented changes in the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
sequence that cause HCP include missense
Missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
, nonsense
Nonsense mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...
, deletion
Genetic deletion
In genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome...
and splicing
Splicing (genetics)
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...
of single nucleotides. Documented changes in the protein sequence have been a replacement of ser208 to phe(s208f) and arg328 to cys(r328c). Aside from varying intensity of symptoms there are no other known mutations, and it is not known at this time if mutations in other genes can trigger this same disease. At this time it is not known if there are any specific groups of people that are especially susceptible to this disease, as patients have been documented all over the world.
Molecular biology
The CPO gene is located in chromosome 3 on the q12 locus. The gene is 14,000 bases in length, has 6 intronIntron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
s, and 7 exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
s. Once the introns are spliced out the actual coded mRNA is only 2675 bases in length. The protein contains 323 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s.
Function
The coproporphinogen oxidase gene is an enzyme expressed in erythrocytes that converts coproporphyrinogen III to protoporphyrinogen IX. HemeHeme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
is made from porphyrin and when a mutation occurs, heme production is interrupted. This leads to an overabundance of porphyrin in the body, which then exits through urine/feces.