Lecture 8 (Part 1) Porphyrias

Haem synthesis occurs in the cytosol and mitochondria;

In immature erythrocytes (reticulocytes), haem stimulates protein synthesis of the globin chains and erythropoietin stimulates haem The kidney releases erythropoietin hormone at low oxygen levels in tissues and stimulates RBC and haemoglobin synthesis.

haem synthesis stops when haem is not incorporated into proteins and when haem and hemin accumulate.

The porphyrias are a group of seven rare diseases characterized by chronic skin manifestations (cutaneous porphyrias) or by intermittent acute attacks of illness (acute porphyrias). A group of disorders caused by deficiencies of enzymes involved in the production of haem.

Acute porphyrias: Porphyrias that cause neurologic, mental, and abdominal symptoms Cutaneous porphyrias: Porphyrias that cause skin symptoms when the skin is exposed to sunlight

Based on where excess precursors orginate Hepatic porphyrias: Precursors originate primarily in the liver Erythropoietic porphyrias: Precursors originate primarily in the bone marrow

Lecture Slide

Acute intermittent Variegate porphyria (VP) Hereditary coproporphyria (HP)

When exposed to light and oxygen, these porphyrins generate an unstable form of oxygen capable of damaging the skin • Porphyria cutanea tarda (PCT), the most common cutaneous porphyria • Congenital erythropoietic porphyria (CEP) • Hepatoerythropoietic porphyria (HEP)

Acute intermittent hereditary coproporphyria variegate porphyria.

• ALAD deficiency porphyria, • congenital erythropoietic porphyria • Hepatoerythropoietic porphyria • erythropoietic protoporphyria.

Cutaneous Tarda

Measuring porphyrins and porphyrin precursors in the urine, faeces or blood symptoms: Acute attacks of severe abdominal pain, nausea, vomiting, rapid heartbeat and other symptoms. test: Spot urine porphobilinogen (PBG) and total porphyrins* symptoms: Blistering skin photosensitivity (with or without acute attack symptoms) Test: plasma or urine total porphyrins

• Stool Porphyrins Once a diagnosis of acute porphyria has been made, used to differentiate HCP, VP and AIP Total Plasma Porphyrins differentiate VP from other porphyria Erythrocyte Porphyrins differentiate PCT from HEP and CEP

Nonspecific symptoms: symptoms of an acute attack can be caused by many other things Variable symptoms: no single symptom or constellation of symptoms is universal in all patients Missing or incomplete Family History: about 1/3 of the time, there is no family history of the disease because the disease has been latent for several generations Wrong tests are ordered and/or test results are not available promptly because they cannot be done on site

Prompt diagnosis is important because delays can result in irreversible neurologic damage Many of the medications used to treat the nonspecific symptoms of porphyria are drugs that can precipitate or worsen acute attacks Untreated attacks can result in long-term or permanent paralysis, coma, neurological damage, or even death

u Use light-proof bottle (wrap it in aluminum foil.) Urine should be alkalinized and refrigerated.

1.Porphobilinogen recommended when AIP, HCP, or VP is suspected 2.Urine Porphyrin Fractionation and Quantitation used to evaluate patients for porphyrias that manifest with blistering cutaneous photosensitivity. 3.Erythrocyte Porphyrin (red cell) first-line test for evaluating patients for suspected protoporphyrias (EPP )