Porphyrias

The porphyrias are inherited disorders. porphyrias are metabolic disorders caused by altered activities of enzymes within the heme biosynthetic pathway

• Acute intermittent porphyria: Pyrroloporphyria; neuropsychiatric–abdominal
• -Aminolevulinic aciduria; neuropsychiatric–abdominal
• Congenital erythropoietic porphyria: Günther disease; severe dermatologic
• Hereditary coproporphyria: Neuropsychiatric, occasionally dermatologic
• Other rare genetic variants reported
• Porphobilinogen synthetase deficiency:
• Porphyria cutanea tarda: Dermatologic
• Protoporphyria: Erythropoietic or hepatoerythropoietic; mild dermatologic
• Variegate porphyria: South African porphyria; prevalence in South Africa is 1/400.

Each involves a specific enzyme of heme bio­synthesis.

Porphyrias are classified as :

• · Hepatic – (neuropathic features)
• · Erythropoietic – (skin involvement).

The hepatic porphyrias present with neurologic features:

• · Neuropathic abdominal pain
• · Neuropat~y
• · Mental disturbances.

The erythropoie.tic porphyrias present with:

• · Cutaneous sehsitivity
• · Scarring and pigmentation of skin.

Porphyrias Classification of the human porphyrias

• as hepatic or erythropoietic and as acute or cutaneous, the affected enzymes, patterns of inheritance and their major biochemical features

Causes of porphyrias :

• · Environmental
• · Physiological
• · Genetic.
• The porphyrias are diagnosed and classified by chro­matography and demonstration of specific enzyme deficiency or gene defect 

Risk Factors

• Drugs (e.g., barbiturates and sulfas in acute intermittent porphyria)
• Estrogens (especially oral contraceptives)
• Fasting
• Heavy alcohol use
• Hexachlorobenzene exposure
• Infection
• Liver disease
• Multiple precipitating factors, especially in acute intermittent porphyria, variegate porphyria, hereditary coproporphyria
• Steroids

HEPATIC PORPHYRIAS

• There is rapid onset of neurologic manifestations. There is elevated levels of plasma and urinary ALA (Urinary gamma amino levulinic acid and PBG-Por­phobilinogen).

ALA-dehydratase deficient porphyria

• Clinical features are abdominal pain and neuropathy.

Acute intermittent porphyria

•  This is a common porphyria.
• The disease is activated by drugs, low calorie diet, steroids, alcohol.
• It presents with :
• Abdominal pain Diarrhea
• Fever
• Vomiting
• Hypertension
• Pain in the limbs Muscle weakness Mental symptoms Peripheral neuropathy.

Treatment: Narcotic analgesics, IV glucose, phe­nothiazines Porphyria cutanea tarda There is :

• Cutaneous photosensitivity
• Vesicles and bullae on exposed skin Hyperpigmentation
• It is precipitated by alcohol, iron, estrogens Treatment: Repeated phlebotomy (450 ml of blood is removed by cutting a vein), chloroquine, hydrochloroquine(HCQ) .

Hereditary corpoporphyria

• Common in women
• There is photosensitivity of skin

Treatment:

• phlebotomy and chloroquine

Variegate porphyria

• Presents with neurological symptoms and photosen­sitivity
• ERYTHROPOIETIC PORPHYRIAS X-linked sideoblastic anaemia
• There is refractory anaemia, hypersplenism, hemosi­derosis

Treatment: is pyridoXine supplementation

Congenital porphyria

• Also known as Gunther’s Disease.
• Very rare and associated with hemolytic anaemia. Cutaneous lesions – hyperpigmentation, thickening of skin, disfigurement of face and hands.
• Teeth reddish brown.

Treatment:

•  is splenectomy, protection from sun­light, beta carotene, bone marrow transplant, stem cell therapy