Photomutilation and transfusion dependent anemia are common complications. Liver disease is also observed in some cases. It has been reported that early childhood-onset haematological manifestations is a poor prognosis factor.

Case reports suggest that EPP is prevalent globally. The prevalence has been estimated somewhere between 1 in 75,000 and 1 in 200,000 however it has been noted that the prevalence of EPP may be increasing due to a better understanding of the disease and improved diagnosis. An estimated 5,000-10,000 individuals worldwide have EPP. EPP is considered the most common form of porphyria in children. The prevalence in Sweden has been published as 1:180,000.

While inherited deficiencies in uroporphyrinogen decarboxylase often lead to the development of PCT, there are a number of risk factors that can both cause and exacerbate the symptoms of this disease. One of the most common risk factors observed is infection with the Hepatitis C virus. One review of a collection of PCT studies noted Hepatitis C infection in 50% of documented cases of PCT. Additional risk factors include alcohol abuse, excess iron (from iron supplements as well as cooking on cast iron skillets), and exposure to chlorinated cyclic hydrocarbons and Agent Orange.

It can be a paraneoplastic phenomenon.

Porphyria cutanea tarda has a prevalence estimated at approximately 1 in 10,000. An estimated 80% of porphyria cutanea tarda cases are sporadic. The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives.

Erythropoietic porphyria is a type of porphyria associated with erythropoietic cells. In erythropoietic porphyrias, the enzyme deficiency occurs in the red blood cells.

There are three types:

X-linked sideroblastic anemia or "X-linked dominant erythropoietic protoporphyria", associated with ALAS2 (aminolevulinic acid synthase), has also been described. X-linked dominant erythropoietic protoporphyria (XDEPP) is caused by a gain of function mutation in the ALAS2 (5-aminolevulinate synthase) gene; that gene encodes the very first enzyme in the heme biosynthetic pathway. The mutation is caused by a frameshift mutation caused by one of two deletions in the ALAS2 exon 11, either c. 1706-1709 delAGTG or c. 1699-1700 delAT. This alters the 19 and 20 residues of the C-terminal domain thereby altering the secondary structure of the enzyme. The delAT mutation only occurred in one family studied whereas the delAGTG mutation occurred in several genetically distinct families. The delAGTG causes a loss of an α-helix which is replaced by a β-sheet.

Previously known mutations in the ALAS2 resulted in a loss-of-function mutation causing X-linked sideroblastic anemia. Erythropoietic protoporphyria (EPP) has similar symptoms as X-linked dominant erythropoietic protoporphyria but the mutation occurs as a loss-of-function in the FECH (ferrochelatase) enzyme; the very last enzyme in the pathway. All individuals studied presented symptoms without mutations in the FECH enzyme. The patterns of inheritance led the researchers to conclude the mutation must come from an enzyme on the X-chromosome with ALAS2 being the most likely candidate.

X-linked dominant erythropoietic protoporphyria is distinct from EPP in that there is no overload of Fe ions. Additionally, unlike the other condition the arises out of a mutation of the ALAS2 gene, there is no anaemia. XDEPP is characterized by a buildup of protoporphyrin IX caused by in increased level of function in the ALAS2 enzyme. Because there is a buildup of protoporphyrin IX with no malfunction of the FECH enzyme, all the available Fe is used in the production of heme, causing the FECH enzyme to use Zn in its place, causing a buildup of zinc-protoporphyrin IX.

X-linked dominant erythropoietic protoporphyria is a relatively mild version of porphyria with the predominant symptom being extreme photosensitivity causing severe itching and burning sensation of the skin due to the buildup of protoporphyrin IX. One possible treatment was discovered when treating an individual with supplemental iron for a gastric ulcer. Levels of free protoporphyrin decreased significantly as there was iron available for the FECH to produce heme. Levels of zinc-protoporphyrin, however did not decrease.

Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include hemochromatosis and hepatitis C. Treatment of iron overload may be required.

Patients with the acute porphyrias (AIP, HCP, VP) are at increased risk over their life for hepatocellular carcinoma (primary liver cancer) and may require monitoring. Other typical risk factors for liver cancer need not be present.

Hepatic porphyrias is a form of porphyria in which the enzyme deficiency occurs in the liver.

Examples include (in order of synthesis pathway):

- Acute intermittent porphyria

- Porphyria cutanea tarda and Hepatoerythropoietic porphyria

- Hereditary coproporphyria

- Variegate porphyria

Hormonal fluctuations that contribute to cyclical attacks in women have been treated with oral contraceptives and luteinizing hormones to shut down menstrual cycles. However, oral contraceptives have also triggered photosensitivity and withdrawal of oral contraceptives has triggered attacks. Androgens and fertility hormones have also triggered attacks.

In South Africa, the prevalence of variegate porphyria is approximately 1 in 300. In Finland, the prevalence is approximately 1 in 75.000.

When it does occur in other populations (such as Switzerland), it can be with different mutations than in South Africa.

It is also found in Argentina, Sweden, and Australia.

Hereditary coproporphyria (HCP) is a disorder of heme biosynthesis, classified as an acute hepatic porphyria. HCP is caused by a deficiency of the enzyme coproporphyrinogen oxidase, coded for by the "CPOX" gene, and is inherited in an autosomal dominant fashion, although homozygous individuals have been identified. Unlike acute intermittent porphyria, individuals with HCP can present with cutaneous findings similar to those found in porphyria cutanea tarda in addition to the acute attacks of abdominal pain, vomiting and neurological dysfunction characteristic of acute porphyrias. Like other porphyrias, attacks of HCP can be induced by certain drugs, environmental stressors or diet changes. Biochemical and molecular testing can be used to narrow down the diagnosis of a porphyria and identify the specific genetic defect. Overall, porphyrias are rare diseases. The combined incidence for all forms of the disease has been estimated at 1:20,000. The exact incidence of HCP is difficult to determine, due to its reduced penetrance.

Gunther disease, also known as congenital erythropoietic porphyria (CEP), uroporphyrinogen III synthase deficiency and UROS deficiency, is a congenital form of erythropoietic porphyria. The word porphyria originated from the Greek word porphura. Porphura actually means "purple pigment", which, in suggestion, the color that the body fluid changes when a person has Gunther's disease. It is a rare, autosomal recessive metabolic disorder affecting heme, caused by deficiency of the enzyme uroporphyrinogen cosynthetase. It is extremely rare, with a prevalence estimated at 1 in 1,000,000 or less. There have been times that prior to birth of a fetus, Gunther's disease has been shown to lead to anemia. In milder cases patients have not presented any symptoms until they have reached adulthood. In Gunther's disease, porphyrins are accumulated in the teeth and bones and an increased amount are seen in the plasma, bone marrow, feces, red blood cells, and urine.

Variegate porphyria, also known by several other names, is an autosomal dominant porphyria that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect the skin. The disorder results from low levels of the enzyme responsible for the seventh step in heme production. Heme is a vital molecule for all of the body's organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood.

Erythropoietic protoporphyria (EPP) is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the erythrocytes, plasma, skin and liver. The severity varies significantly from individual to individual.

A clinically similar form of porphyria, known as X-Linked dominant protoporphyria, was identified in 2008.

There is no cure for HCP caused by the deficient activity of coproporphyrinogen oxidase. Treatment of the acute symptoms of HCP is the same as for other acute porphyrias. Intravenous hemin (as heme arginate or hematin) is the recommended therapy for acute attacks. Acute attacks can be severe enough to cause death if not treated quickly and correctly. Hospitalization is typically required for administration of hemin, and appropriate drug selection is key to avoid exacerbating symptoms with drugs that interact poorly with porphyrias. 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. Gabapentin and levetiracetam are two anti-seizure drugs that are thought to be safe.

In patients where management of symptoms is difficult even with hemin, liver transplant is an option before the symptoms have progressed to advanced paralysis. Combined liver and kidney transplants are sometimes undertaken in patients with renal failure.

Long term treatment of acute porphyrias is centered on the avoidance of acute attacks by eliminating precipitating factors, such as drugs, dietary changes, and infections. Females often have attacks coincident with their menstrual cycle, which can be managed effectively with hormonal birth control. Because of the reduced penetrance of HCP, family members of a patient may carry the same mutation without ever presenting with symptoms. Molecular analysis of "CPOX" is the best way to identify these patients, as they will not express a biochemical phenotype on laboratory testing unless they are symptomatic. Identification of asymptomatic patients allows them to adjust their lifestyle to avoid common triggering factors.

Aminolevulinic acid dehydratase deficiency porphyria (also known as "Doss porphyria", and "plumboporphyria") is a neuropsychiatric condition, disease can present during early childhood (as well as in adulthood) with acute neurologic symptoms that resemble those encountered in acute intermittent porphyria. The condition is extremely rare, with fewer than 10 cases ever reported.

ALA dehydratase deficiency is a rare cause of hepatic porphyria. It is an autosomal recessive disorder that results from inappropriately low levels of the enzyme ALA dehydratase (ALAD, also called porphobilinogen synthase), which is required for normal heme synthesis.

Harderoporphyria is a rare disorder of heme biosynthesis, inherited in an autosomal recessive manner caused by specific mutations in the "CPOX" gene. Mutations in "CPOX" usually cause hereditary coproporphyria, an acute hepatic porphyria, however the K404E mutation in a homozygous or compound heterozygous state with a null allele cause the more severe harderoporphyria. Harderoporphyria is the first known metabolic disorder where the disease phenotype depended on the type and location of the mutations in a gene associated with multiple disorders.

In contrast with other porphyrias, which typically present with either cutaneous lesions after exposure to sunlight or acute neurovisceral attack at any age (most commonly in adulthood), harderoporphyria is characterized by jaundice, anemia enlarged liver and spleen, often presenting in the neonatal period. Later in life, these individuals may present with photosensitivity similar to that found in cutaneous porphyrias.

Biochemically, harderoporphyria presents with a distinct pattern of increased harderoporphyrin (2-vinyl-4,6,7-tripropionic acid porphyrin) in urine and particularly in feces, a metabolite that is not seen in significant quantities in any other porphyria. Enzyme tests show markedly reduced activity of coproporphyrinogen oxidase, compared to both unaffected individuals and those affected with hereditary coproporphyria, consistent with recessive inheritance.

Harderoporphyria is a rare condition, with less than 10 cases reported worldwide. It may be underdiagnosed, as it does not have the typical presentation associated with a porphyria. It was identified as a variant type of coproporphyria in 1983, in a family with three children identified at birth with jaundice and hemolytic anemia. There is no standard treatment for harderoporphyria; care is mainly focused on the management of symptoms.

ALA dehydratase deficiency is inherited in an autosomal recessive manner. This means a defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Acute intermittent porphyria (AIP) is a genetic metabolic disorder affecting the production of heme, the oxygen-binding prosthetic group of hemoglobin. It is characterized by a deficiency of the enzyme porphobilinogen deaminase. Its inheritance is more commonly autosomal dominant; however, autosomal recessive forms of this disorder have occurred. Its incidence is estimated to be between 5 and 10 in 100,000.

If drugs have caused the attack, discontinuing the offending substances is essential. A high-carbohydrate (10% glucose) infusion is recommended, which may aid in recovery.

Hematin and heme arginate is the treatment of choice during an acute attack. Heme is not a curative treatment, but can shorten attacks and reduce the intensity of an attack. Side-effects are rare but can be serious. Pain is extremely severe and almost always requires the use of opiates to reduce it to tolerable levels. Pain should be treated as early as medically possible due to its severity.

Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot water baths or showers may lessen nausea temporarily, but can present a risk of burns or falls.

Seizures often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: Barbiturates and Primidone must be avoided as they commonly precipitate symptoms. Some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control.

Hepatoerythropoietic porphyria is a very rare form of hepatic porphyria caused by a disorder in both genes which code Uroporphyrinogen III decarboxylase (UROD).

It has a similar presentation to porphyria cutanea tarda (PCT), but with earlier onset. In classifications which define PCT type 1 as "sporadic" and PCT type 2 as "familial", hepatoerythropoietic porphyria is more similar to type 2.

Sun avoidance, avoidance of tanning booths, and usage of broad spectrum sunscreen that blocks both UVA and UVB.

Identification and avoidance of the offending drug.

The precise pathophysiologic mechanism of pseudoporphyria is not fully understood. Some drugs, especially non steroidal anti-inflammatory drugs, can trigger pseudoporphyria in the presence of ultraviolet light.

The pathophysiology of pseudoporphyria associated with hemodialysis has not been fully explained. Aluminum hydroxide has been implicated in hemodialysis-associated pseudoporphyria. Aluminum hydroxide is found in dialysis solution and has been shown to produce a porphyrialike disorder after long-term administration in rats.

Anemia of prematurity refers to a form of anemia affecting preterm infants with decreased hematocrit.

Urbach–Wiethe disease is very rare; there are fewer than 300 reported cases in medical literature. Although Urbach–Wiethe disease can be found worldwide, almost a quarter of reported diagnoses are in South Africa. Many of these are in patients of Dutch, German, and Khoisan ancestry. This high frequency is thought to be due to the founder effect. Due to its recessive genetic cause and the ability to be a carrier of the disease without symptoms, Urbach–Wiethe disease often runs in families. In some regions of South Africa, up to one in 12 individuals may be carriers of the disease. Most of the case studies involving Urbach–Wiethe disease patients involve only one to three cases and these cases are often in the same family. Due to its low incidence, it is difficult to find a large enough number of cases to adequately study the disease.

Preterm infants are often anemic and typically experience heavy blood losses from frequent laboratory testing in the first few weeks of life. Although their anemia is multifactorial, repeated blood sampling and reduced erythropoiesis with extremely low serum levels of erythropoietin (EPO) are major determining factors. Blood sampling done for laboratory testing can easily remove enough blood to produce anemia. Obladen, Sachsenweger and Stahnke (1987) studied 60 very low birth weight infants during the first 28 days of life. Infants were divided into 3 groups, group 1 (no ventilator support, 24 ml/kg blood loss), group 2(minor ventilated support, 60 ml/kg blood loss), and group 3(ventilated support for respiratory distress syndrome, 67 ml/kg blood loss). Infants were checked for clinical symptoms and laboratory signs of anemia 24 hours before and after the blood transfusion. The study found that groups 2 and 3 who had significant amount of blood loss, showed poor weight gain, pallor and distended abdomen. These reactions are the most frequent symptoms of anemia.

During the first weeks of life, all infants experience a decline in circulating red blood cell (RBC) volume generally expressed as blood hemoglobin concentration (Hb). As anemia develops, there is even more of a significant reduction in the concentration of hemoglobin. Normally this stimulates a significant increased production of erythropoietin (EPO), but this response is diminished in premature infants. Dear, Gill, Newell, Richards and Schwarz (2005) conducted a study to show that there is a weak negative correlation between EPO and Hb. The researchers recruited 39 preterm infants from 10 days of age or as soon as they could manage without respiratory support. They estimated total EPO and Hb weekly and 2 days after a blood transfusion. The study found that when Hb>10, EPO mean was 20.6 and when Hb≤10, EPO mean was 26.8. As Hb goes down, EPO goes up. While the reason for this decreased response is not fully understood, Strauss (n.d.) states that it results from both physiological factors (e.g., the rapid rate of growth and need for a commensurate increase in RBC mass to accompany the increase in blood volume) and, in sick premature infants, from phlebotomy blood losses. In premature infants this decline occurs earlier and more pronounced that it does in healthy term infants. Healthy term infants Hb rarely falls below 9 g/dL at an age of approximately 10–12 weeks, while in premature infants, even in those without complicating illnesses, the mean Hb falls to approximately 8g/dL in infants of 1.0-1.5 kg birth weight and to 7g/dL in infants <1.0 kg. Because this postnatal drop in hemoglobin level is universal and is well tolerated in term infants, it is commonly referred to as the “physiologic” anemia of infancy. However, in premature infants the decline in Hb may be associated with abnormal clinical signs severe enough to prompt transfusions.