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Hepatic Porphyria

Updated : February 13, 2024





Background

The 8 enzymes involved in the hemoglobin biosynthesis pathway are all defective in the group of metabolic diseases known as porphyrias, which causes an overproduction of porphyrins, an organic molecule. The typical biochemical and clinical profile for every porphyria follows from this. Porphyrias with an enzyme deficit in the hepatic are referred to as hepatic porphyrias.

Acute intermittent porphyria, hereditary coproporphyria, aminolevulinic acid dehydratase deficit porphyria, variegate porphyria, and PCT (porphyria cutanea tarda) are hepatic porphyrias. Although these situations are different, they share an aggregation of hemoglobin precursors.

The increased generation of neurotoxin precursors appears to be the cause of symptoms in acute porphyrias, which largely damage the nerves. The accumulation of photosensitizer porphyrins in the dermis appears to be the primary cause of symptoms in chronic porphyrias, which primarily present as skin lesions.

Some porphyria kinds can manifest cutaneously and neurologically. In order to stop the symptoms from getting worse, injectable hemin is given as treatment. Patients who experience acute episodes or symptom progression despite hemin treatment are only eligible for LT (liver transplantation).

Epidemiology

A rough estimate of the incidence of porphyria in the U.s is one in every 25,000 people. It is estimated that between 1 in 500 and 1 in 50,000 people globally have the condition. Acute liver porphyria affects people of all races and ethnicities. Acute intermittent porphyria is the most prevalent, while aminolevulinic acid dehydratase deficit porphyria is the least prevalent in the majority of locations.

According to reports, there are five to ten cases of clinical acute intermittent porphyria for every 100,000 people, and 1 in 1675 people has an acute intermittent porphyria genetic variant. The prevalence of variegate porphyria, which is more uncommon, has been estimated to be 3 symptomatic instances per million people, with a reported prevalence of four to thirteen cases per 1,00,000 people.

It should be noted that while being autosomal dominant illnesses, acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria are likely to affect both women and men equally. Acute intermittent porphyria has nonetheless shown a bias against women, with reporting of incidents being 5 times more common in non-Latino women than in men.

Anatomy

Pathophysiology

Heme, a crucial component of heme, catalase, P450 cytochromes, and myoglobin, is primarily produced by porphyrins. The porphyrin pathway’s enzymes are missing in porphyrias, leading to unusually high amounts of this hemoglobin progenitor that are hazardous to structures at large levels.

The place of accumulation and, eventually, the medical symptoms are governed by the chemical characteristics of these byproducts. The heme biosynthesis pathway consists of eight enzymes, 4 of which are found in the mitochondrial as well as four in the cytoplasm.

Porphyria can be caused by flaws in any one of these proteins. Psychosis, seizures, acute polyneuropathy, severe back and stomach pain, and, to a smaller extent, cutaneous signs, most frequently hypertrichosis or a photosensitive blister rash, are neurological assaults that characterize the acute hepatic porphyrias.

Etiology

Generally speaking, porphyrias are regarded as inherited illnesses. Depending on which enzyme is lacking, the majority of kinds are brought on by a mutation in a gene that makes heme. The different porphyrias are inherited from one’s parents and can occur in an X-linked, AD (autosomal dominant), or AR (autosomal recessive) manner.

A few AD disorders that equally affect men and women are AIP (acute intermittent porphyria), VP (variegate porphyria), and HCP (hereditary coproporphyria). A relatively uncommon AR disorder called aminolevulinic acid dehydratase deficiency porphyria (ALAD) is the fourth kind.

Several abnormalities have been discovered in genetic research using DNA testing for the 3 AD types. The underlying mechanism causes an increase in heme precursors and a decrease in the amount of heme synthesized. A number of medications, many of which are suspected to interact with liver enzymes involved in heme production, can also cause acute hepatic porphyria.

Genetics

Prognostic Factors

Data on the prognosis of people with acute hepatic porphyria are few because of their uncommon and poor penetrance. Patients who have severe clinical symptoms have an elevated risk of mortality.

However, people with modest clinical characteristics might never receive a diagnosis, which would result in an incorrect overestimation of mortality. Patients who receive quick diagnosis and treatment for acute attacks may have a fair prognosis, particularly if their condition is still latent.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK537178/

Hepatic Porphyria

Updated : February 13, 2024




The 8 enzymes involved in the hemoglobin biosynthesis pathway are all defective in the group of metabolic diseases known as porphyrias, which causes an overproduction of porphyrins, an organic molecule. The typical biochemical and clinical profile for every porphyria follows from this. Porphyrias with an enzyme deficit in the hepatic are referred to as hepatic porphyrias.

Acute intermittent porphyria, hereditary coproporphyria, aminolevulinic acid dehydratase deficit porphyria, variegate porphyria, and PCT (porphyria cutanea tarda) are hepatic porphyrias. Although these situations are different, they share an aggregation of hemoglobin precursors.

The increased generation of neurotoxin precursors appears to be the cause of symptoms in acute porphyrias, which largely damage the nerves. The accumulation of photosensitizer porphyrins in the dermis appears to be the primary cause of symptoms in chronic porphyrias, which primarily present as skin lesions.

Some porphyria kinds can manifest cutaneously and neurologically. In order to stop the symptoms from getting worse, injectable hemin is given as treatment. Patients who experience acute episodes or symptom progression despite hemin treatment are only eligible for LT (liver transplantation).

A rough estimate of the incidence of porphyria in the U.s is one in every 25,000 people. It is estimated that between 1 in 500 and 1 in 50,000 people globally have the condition. Acute liver porphyria affects people of all races and ethnicities. Acute intermittent porphyria is the most prevalent, while aminolevulinic acid dehydratase deficit porphyria is the least prevalent in the majority of locations.

According to reports, there are five to ten cases of clinical acute intermittent porphyria for every 100,000 people, and 1 in 1675 people has an acute intermittent porphyria genetic variant. The prevalence of variegate porphyria, which is more uncommon, has been estimated to be 3 symptomatic instances per million people, with a reported prevalence of four to thirteen cases per 1,00,000 people.

It should be noted that while being autosomal dominant illnesses, acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria are likely to affect both women and men equally. Acute intermittent porphyria has nonetheless shown a bias against women, with reporting of incidents being 5 times more common in non-Latino women than in men.

Heme, a crucial component of heme, catalase, P450 cytochromes, and myoglobin, is primarily produced by porphyrins. The porphyrin pathway’s enzymes are missing in porphyrias, leading to unusually high amounts of this hemoglobin progenitor that are hazardous to structures at large levels.

The place of accumulation and, eventually, the medical symptoms are governed by the chemical characteristics of these byproducts. The heme biosynthesis pathway consists of eight enzymes, 4 of which are found in the mitochondrial as well as four in the cytoplasm.

Porphyria can be caused by flaws in any one of these proteins. Psychosis, seizures, acute polyneuropathy, severe back and stomach pain, and, to a smaller extent, cutaneous signs, most frequently hypertrichosis or a photosensitive blister rash, are neurological assaults that characterize the acute hepatic porphyrias.

Generally speaking, porphyrias are regarded as inherited illnesses. Depending on which enzyme is lacking, the majority of kinds are brought on by a mutation in a gene that makes heme. The different porphyrias are inherited from one’s parents and can occur in an X-linked, AD (autosomal dominant), or AR (autosomal recessive) manner.

A few AD disorders that equally affect men and women are AIP (acute intermittent porphyria), VP (variegate porphyria), and HCP (hereditary coproporphyria). A relatively uncommon AR disorder called aminolevulinic acid dehydratase deficiency porphyria (ALAD) is the fourth kind.

Several abnormalities have been discovered in genetic research using DNA testing for the 3 AD types. The underlying mechanism causes an increase in heme precursors and a decrease in the amount of heme synthesized. A number of medications, many of which are suspected to interact with liver enzymes involved in heme production, can also cause acute hepatic porphyria.

Data on the prognosis of people with acute hepatic porphyria are few because of their uncommon and poor penetrance. Patients who have severe clinical symptoms have an elevated risk of mortality.

However, people with modest clinical characteristics might never receive a diagnosis, which would result in an incorrect overestimation of mortality. Patients who receive quick diagnosis and treatment for acute attacks may have a fair prognosis, particularly if their condition is still latent.

https://www.ncbi.nlm.nih.gov/books/NBK537178/