PORPHYRIAS CAUSES

General characteristics

The underlying cause of all porphyrias is a defective enzyme somewhere along the heme biosynthesis pathway. In virtually all cases, the defective enzyme is a genetically linked factor. Therefore, porphyrias are inheritable conditions. However, an environmental trigger--such as diet, drugs, or sun exposure--may be necessary before any symptoms develop. In many cases, symptoms do not develop, and people may be completely unaware that they have a gene for porphyria.

All of the hepatic porphyrias--except porphyria cutanea tarda--follow a pattern of acute attacks interspersed among periods of complete symptom remission. For this reason, they are often referred to as the acute porphyrias. The erythropoietic porphyrias and porphyria cutanea tarda do not follow the same pattern and are considered chronic conditions.

The specific symptoms of each porphyria depend on the affected enzyme and whether it occurs in the liver or in the bone marrow. The severity of symptoms can vary widely, even within the same porphyria type. If the porphyria becomes symptomatic, the common factor between all types is an abnormal accumulation of protoporphyrins or porphyrin.

ALA dehydratase porphyria (ADP)

ADP is characterized by a deficiency of ALA dehydratase. Of the few cases on record, the prominent symptoms were vomiting, pain in the abdomen, arms, and legs, and neuropathy. (Neuropathy refers to nerve damage that can cause pain, numbness, or paralysis.) Owing to the neuropathy, the arms and legs may be weak or paralyzed and breathing can be impaired.

Acute intermittent porphyria (AIP)

AIP is caused by a deficiency in porphobilogen deaminase, but symptoms usually don't occur unless a person with the deficiency encounters a trigger substance. Such substances can include hormones (for example oral contraceptives, menstruation, pregnancy), drugs, and dietary factors. However, most people with the deficiency never develop symptoms.

Attacks occur after puberty and commonly feature severe abdominal pain, nausea and vomiting, and constipation. Muscle weakness and pain in the back, arms, and legs are also typical symptoms. During an attack, the urine takes on a deep reddish color. The central nervous system may also be involved, as demonstrated by hallucinations, confusion, seizures, and mood changes.

Congenital erythropoietic porphyria (CEP)

CEP arises from a deficiency in uroporphyrinogen III cosynthase. Symptoms are often apparent in infancy and include reddish urine and possibly an enlarged spleen. The skin is unusually sensitive to light and blisters easily if exposed to sunlight. (Sunlight induces changes in protoporphyrins in the plasma and skin. These altered molecules can damage the skin.) Increased hair growth is common. Damage from recurrent blistering and associated skin infections can be severe; in some cases facial features and fingers are lost to recurrent damage and infection. Deposits of protoporphyrins sometimes occur in the teeth and bones.

Porphyria cutanea tarda (PCT)

PCT is caused by deficient uroporphyrinogen decarboxylase; it may be an acquired or inherited condition. The acquired form usually does not appear until adulthood. The inherited form may appear in childhood, but often demonstrates no symptoms. Early symptoms include blistering on the hands, face, and arms following minor injuries or exposure to sunlight. Lightening or darkening of the skin may occur along with increased hair growth or loss of hair. Liver function is abnormal but the signs are mild.

Hepatoerythopoietic porphyria (HEP)

HEP is linked to a deficiency of uroporphyrinogen decarboxylase in both the liver and the bone marrow. The symptoms resemble those of CEP.

Hereditary coproporphyria (HCP)

HCP is similar to AIP, but the symptoms are typically more mild; the disorder is caused by a deficiency in coproporphyrinogen oxidase. The greatest difference between HCP and AIP is that people with HCP may have some skin sensitivity to sunlight. However, extensive damage to the skin is rarely seen.

Variegate porphyria (VP)

VP is caused by deficient protoporphyrinogen oxidase, and, like AIP, symptoms only occur during attacks. Major symptoms of this type of porphyria involve neurologic problems and sensitivity to light. Areas of the skin that are exposed to sunlight are susceptible to burning, blistering, and scarring.

Erythropoietic protoporphyria (EPP)

Owing to deficient ferrochelatase, the last step in the heme biosynthesis pathway--the insertion of an iron atom into a porphyrin molecule--cannot be completed. The major symptoms of this disorder are related to sensitivity to light--including both artificial and natural light sources. Following exposure to light, a person with EPP experiences burning, itching, swelling, and reddening of the skin. Blistering and scarring may occur but are neither common nor severe. EPP may result in the formation of gallstones as well as liver complications. Symptoms can appear in childhood and tend to be more severe during the summer when exposure to sunlight is more likely.

PORPHYRIAS RELATED ITEMS

	PORPHYRIAS DEFINITION
	PORPHYRIAS DESCRIPTION
	PORPHYRIAS CAUSES
	PORPHYRIAS SYMPTOMS
	PORPHYRIAS DIAGNOSIS
	PORPHYRIAS TREATMENTS
	PORPHYRIAS PROGNOSIS
	PORPHYRIAS INFORMATION
	PORPHYRIAS PREVENTION