Porphyrias Inherited disorders Causes Classifications Diagnosis and Treatment

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.
Porphyrias

Porphyrias Inherited disorders Causes Classifications Diagnosis and Treatment

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 chrmatography and demonstration of specific enzyme deficiency or gene defec
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

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