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
|Disease||Classification||Enzyme affected*||Inheritance||Major biochemical findings|
|Tissue site||Clinical features||Urine||Plasma||Erythrocytes||Feces|
|-minolevulinic acid dehydratase porphyria (ADP)||Hepatic||Acute||ALAD||Autosomal recessive||ALA, copro-porphyrin III||ALA, copro-porphyrin III||Zinc proto-porphyrin & low ALAD activity|
|Acute intermittent porphyria (AIP)||Hepatic||Acute||PBGD||Autosomal dominant||ALA, PBG, copro-porphyrin||Low PBGD activity|
|Hereditary coproporphyria (HCP)||Hepatic||Acute & cutaneous||CPO||Autosomal dominant||ALA, PBG, copro-porphyrin III||Copro-porphyrin III|
|Variegate porphyria (VP)||Hepatic||Acute & cutaneous||PPO||Autosomal dominant||ALA, PBG, copro-porphyrin III||Fluorescence peak at 626 nm||Copro-porphyrin III & protoporphyrin|
|Porphyria cutanea tarda (PCT)||Hepatic||Cutaneous||UROD||Autosomal dominant||Uroporphyrin & hepta-carboxyl-porpyrin||Uroporphyrin & hepta-carboxyl-porpyrin||Isocopro-porphyrin|
|Hepato-erythropoietic porphyria (HEP)||Hepatic||Cutaneous||UROD||Autosomal recessive||Uroporphyrin & hepta-carboxyl-porpyrin||Uroporphyrin & hepta-carboxyl-porpyrin||Zinc proto-porphyrin & low UROD activity||Isocopro-porphyrin|
|Congenital erythropoietic porphyria (CEP)||Erythro-poietic||Cutaneous||UROS||Autosomal recessive||Uroporphyrin I & copro-porphyrin I||Uroporphyrin I & copro-porphyrin I||Uroporphyrin I & copro-porphyrin I||Copro-porphyrin I|
|Erythropoietic protoporphyria (EPP) – classic form||Erythro-poietic||Cutaneous||FECH||Autosomal dominant||Protoporphyrin||Free protoporphyrin||Protoporphyrin|
|EPP – variant form||Erythro-poietic||Cutaneous||ALAS2||X-linked recessive||Protoporphyrin||Free & zinc protoporphyrin||Protoporphyrin|
Causes of porphyrias :
- · Environmental
- · Physiological
- · Genetic.
- The porphyrias are diagnosed and classified by chromatography and demonstration of specific enzyme deficiency or gene defect
- Drugs (e.g., barbiturates and sulfas in acute intermittent porphyria)
- Estrogens (especially oral contraceptives)
- Heavy alcohol use
- Hexachlorobenzene exposure
- Liver disease
- Multiple precipitating factors, especially in acute intermittent porphyria, variegate porphyria, hereditary coproporphyria
- 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
- 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) .
- Common in women
- There is photosensitivity of skin
- phlebotomy and chloroquine
- Presents with neurological symptoms and photosensitivity
- ERYTHROPOIETIC PORPHYRIAS X-linked sideoblastic anaemia
- There is refractory anaemia, hypersplenism, hemosiderosis
Treatment: is pyridoXine supplementation
- 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.
- is splenectomy, protection from sunlight, beta carotene, bone marrow transplant, stem cell therapy