Hepatoerythropoietic Porphyria

Hepatoerythropoietic Porphyria

Brain & Nerve
Digestive Health
Contributed byLester Fahrner, MD+1 moreJul 25, 2022

What are the other Names for the Condition? (Also known as/Synonyms)

  • Autosomal Recessive PCT
  • Autosomal Recessive Porphyria Cutanea Tarda
  • Familial Porphyria Cutanea Tarda (f-PCT)

What is Hepatoerythropoietic Porphyria? (Definition/Background Information)

  • Porphyrias are disorders resulting from excess porphyrin buildup in the liver and bone marrow. Manufacturing hemoglobin and related proteins (heme synthesis) involves a class of molecules called porphyrins. Porphyrias are either inherited or acquired, and are described as acute, chronic, and cutaneous
  • Hepatoerythropoietic Porphyria (HEP) is a very rare form of hepatic porphyria that manifests as a skin condition. In this condition, the skin is severely sensitive to light, which often presents as blistering, scarring, and severe disfigurement
  • Hepatoerythropoietic Porphyria is described as the familial form of Porphyria Cutanea Tarda (or f-PCT). It is a genetic condition that is inherited in an autosomal recessive manner; the involvement of the UROD gene is noted. The onset of symptoms mostly occurs in early childhood
  • A healthcare provider typically diagnoses this genetic disorder by testing blood or other bodily fluids of the affected individual for porphyrin compounds, as well as  gene mutations
  • The treatments for Hepatoerythropoietic Porphyria can include the use of anti-malarial drugs in low doses and active sun protection. The prognosis is determined by the severity of symptoms and it is variable

Who gets Hepatoerythropoietic Porphyria? (Age and Sex Distribution)

  • Hepatoerythropoietic Porphyria (HEP) is described as a rare variant of Porphyria Cutanea Tarda (PCT), with fewer than 50 cases being recorded in the medical literature
  • Generally, the onset of symptoms occurs during infancy or early childhood (within the first 2 years). However, in case the condition is not severe, HEP may be diagnosed only in adulthood
  • The disorder occurs without gender, racial, or ethnic bias

What are the Risk Factors for Hepatoerythropoietic Porphyria? (Predisposing Factors)

  • A family history of Hepatoerythropoietic Porphyria increases the risk of a newborn being diagnosed with the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hepatoerythropoietic Porphyria? (Etiology)

Hepatoerythropoietic Porphyria is caused by mutations in the UROD gene, which is necessary to produce “heme”. The condition is inherited in an autosomal recessive manner. The gene is located on the short arm of chromosome 1.

  • Heme is a critical component of iron-containing proteins called hemoproteins. Hemoglobin is one such protein, which is the oxygen carrier in blood. Blood, bone marrow, and liver have the most heme protein in them
  • Mutations in the defective gene affects porphyrin metabolism. A compromised porphyrin metabolism causes a buildup of porphyrins in the body
  • The enzyme involved in end heme synthesis, called uroporphyrinogen decarboxylase (UROD), is affected and dysfunctional. This enzyme is in the liver and to some extent in red blood cells
  • When the activity and levels of UROD is affected, it leads to abnormal and excess collection of porphyrin compounds in skin, liver, red blood cells, and bone marrow. These compounds react with light energy resulting in skin symptoms, termed photosensitivity. In HEP, the photosensitivity of skin can be mild or severe (observed in most cases)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Hepatoerythropoietic Porphyria?

The signs and symptoms of Hepatoerythropoietic Porphyria can vary in severity from one individual to another. Typically, chronic blistering of the skin on exposure to sunlight in young children, is reported to be a characteristic and identifying feature of HEP.

The signs and symptoms may include the following:

  • On exposure to sunlight, the skin gets inflamed with burning sensation; often, the photosensitivity is severe and chronic
  • Blistering of the skin and formation of blisters (vesicles) on skin
  • In some infants and children, tiny skin bumps resembling milia may be observed
  • Recurrent skin infections
  • Skin ulceration resulting in scarring of the skin
  • Hyperpigmentation or hypopigmentation may be seen (increased or decreased skin pigmentation)
  • Sun-exposed areas of the body are affected the most, such as the face, neck, shoulders, arms (including the wrists and fingers), and chest and back
  • Weak and fragile skin that is easily damaged on minor trauma or injury
  • Increased hair growth or hirsutism; hypertrichosis (or abnormal hair growth) on the affected sun exposed skin areas

The skin signs and symptoms may be non-specific and can be associated with many other skin disorders, such as solar urticaria, epidermolysis bullosa, drug-induced light-sensitivity skin conditions, and other porphyrias that present skin symptoms. Hence, a differential diagnosis is normally undertaken.

Other signs and symptoms of HEP may include:

  • Abnormal color of urine (reddish)
  • Hemolytic anemia (destruction of red blood cells)
  • Red staining of the teeth
  • Inflammation of the liver
  • Splenomegaly (spleen enlargement)
  • Neurological symptoms including peripheral neuropathy, muscular pain, and weak muscles

How is Hepatoerythropoietic Porphyria Diagnosed?

The diagnosis of Hepatoerythropoietic Porphyria is made by the following tools:

  • A complete physical examination and an assessment of symptoms
  • An evaluation of the affected individual’s full medical history
  • Measurement of the porphyrin levels in blood, urine, or feces: Excess amounts of porphyrin compounds (uroporphyrins) are produced, and therefore, seen in urine and feces
  • Measurement of uroporphyrinogen decarboxylase (UROD) enzyme activity
  • Molecular genetic testing before or after birth, to confirm UROD gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hepatoerythropoietic Porphyria?

The potential complications of Hepatoerythropoietic Porphyria may include:

  • Severe skin symptoms on sun exposure include erosion and disfigurement. The disfigurement may involve protruding body parts (appendages), such as the ears, nose and lips, and result in their complete erosion over time
  • Shortening of the fingers and toes
  • Dental and vision abnormalities
  • Anemia and other conditions, due to low levels of oxygen transport. Severe anemia may result in pale skin, weakness, cold hands and feet, and tiredness
  • Severe emotional stress due to cosmetic concerns
  • Bacterial infections following characteristic blistering of the skin

How is Hepatoerythropoietic Porphyria Treated?

A multidisciplinary approach with a team of healthcare specialists and experts from various medical fields may be necessary to treat the condition at a healthcare institution that has the experience and expertise in dealing with porphyrias. No specific treatment measures of Hepatoerythropoietic Porphyria are recognized, but symptomatic treatment is often provided that may include:

  • Use of oral anti-malarial drug chloroquine (low-dose) may be effective in removing excess buildup of porphyrins in liver
  • Avoiding direct exposure to sunlight through:
    • Use of wide-brimmed hats, umbrellas, double-layer clothing, full-sleeved and full pant clothing (made using approved fabric material)
    • Use of UV-protected sunglasses to reduce light-sensitivity
    • Tinted window glasses to protect from sun, both at home and workplaces
    • Use of vinyl coatings on automobile windows
    • The application of topical sunscreen creams is generally found to be ineffective
  • Certain tanning creams and lotions may mitigate the effect of sunlight
  • Treatment of severe anemia that may include blood transfusions and recombinant erythropoietin, which is reported to be effective
  • A splenectomy (removal of the spleen) to alleviate bleeding and worsening anemia (due to spleen enlargement)
  • Undertaking treatment for liver disorders
  • Vitamin and mineral supplementation
  • Newer treatment techniques such as gene therapy
  • Regular blood transfusions, although these are not found to be so effective for HEP, unlike other porphyria forms

Newer medications to alter the effects of abnormal proteins using RNA interference (RNAi) and other molecular technologies are in various stages of development and commercialization. The medical provider may help with information on advancements in new treatment methods.

How can Hepatoerythropoietic Porphyria be Prevented?

Currently, there are no specific methods or guidelines to prevent Hepatoerythropoietic Porphyria, since it is a genetic condition.

  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Hepatoerythropoietic Porphyria

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Hepatoerythropoietic Porphyria? (Outcomes/Resolutions)

  • The prognosis of Hepatoerythropoietic Porphyria varies with the severity of the condition. It is assessed on a case-by-case basis
  • Individuals with mild conditions generally have a better prognosis than those with severe symptoms

Additional and Relevant Useful Information for Hepatoerythropoietic Porphyria:

Porphyria cutanea tarda (PCT) is the most common form of porphyria that manifests almost only as a skin condition (it is a form of cutaneous porphyria).

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On the Article

Krish Tangella MD, MBA picture
Approved by

Krish Tangella MD, MBA

Pathology, Medical Editorial Board, DoveMed Team
Lester Fahrner, MD picture
Reviewed by

Lester Fahrner, MD

Chief Medical Officer, DoveMed Team


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