Pestle Analysis for "Bric" Countries
The porphyrias: inherited disorders of haem synthesis
Michael N. Badminton and George H. Elder
Introduction and overview 558 Porphyrias presenting with acute attacks Biochemistry of haem synthesis
563
The cutaneous porphyqa~, 568 New approaches to treatment 574 Secondary disorders of porphyrin metabolism Conclusion 575 Further reading 575 Appendix 576
574
that result from inherited or acquired partial deficiencies of enzymes of the haem biosynthetic pathway (Fig. 27.1, Table 27.1). The first enzyme of the pathway, 5-aminolaevulinic acid (ALA) synthase (ALAS) is not associated with a porphyria although mutations in the erythroid-specific ALAS (AlAS2) gene cause an X-linked sideroblastic anaemia. However, no disease has yet been associated with defects in the ubiquitous AlASI gene. Porphyria is one of the better known inherited metabolic diseases in .the UK, largely because of various television documentaries and the film The Madness of King George (1994, Director: Nicholas Hytner) in which it was proposed that King George ID suffered from variegate porphyria. Unfortunately,. they ~ve also contribUted to a common misconception that acute porphyria is a cause of chronic psychiatric illness, leading to stress and stigmatization of patients with porphyria. The principal clinical features of the porphyrias are neurovisceral or cutaneous, or both. This chapter approaches the subject ·": from a practical perspective, describing how and why patients present, how they are diagnosed and how patients and their families should be m.aOaged. A list of frequently used abbreviations is provided in Box 27.1.
INTRODUCTION AND OVERVIEW The porphyrias are a group of seven metabolic disorders
Haem is essential for life and is synthesized in all cells, although the major sources are bone marrow (80%) and the· liver (15%). Haemoproteins include haemoglobin and myoglobin, which are the most abundant, the mitochondrial respiratory cytochromes, enzymes such as catalase
Michael N. Badminton and George H. Elder
Introduction and overview 558 Porphyrias presenting with acute attacks Biochemistry of haem synthesis
563
The cutaneous porphyqa~, 568 New approaches to treatment 574 Secondary disorders of porphyrin metabolism Conclusion 575 Further reading 575 Appendix 576
574
that result from inherited or acquired partial deficiencies of enzymes of the haem biosynthetic pathway (Fig. 27.1, Table 27.1). The first enzyme of the pathway, 5-aminolaevulinic acid (ALA) synthase (ALAS) is not associated with a porphyria although mutations in the erythroid-specific ALAS (AlAS2) gene cause an X-linked sideroblastic anaemia. However, no disease has yet been associated with defects in the ubiquitous AlASI gene. Porphyria is one of the better known inherited metabolic diseases in .the UK, largely because of various television documentaries and the film The Madness of King George (1994, Director: Nicholas Hytner) in which it was proposed that King George ID suffered from variegate porphyria. Unfortunately,. they ~ve also contribUted to a common misconception that acute porphyria is a cause of chronic psychiatric illness, leading to stress and stigmatization of patients with porphyria. The principal clinical features of the porphyrias are neurovisceral or cutaneous, or both. This chapter approaches the subject ·": from a practical perspective, describing how and why patients present, how they are diagnosed and how patients and their families should be m.aOaged. A list of frequently used abbreviations is provided in Box 27.1.
INTRODUCTION AND OVERVIEW The porphyrias are a group of seven metabolic disorders
Haem is essential for life and is synthesized in all cells, although the major sources are bone marrow (80%) and the· liver (15%). Haemoproteins include haemoglobin and myoglobin, which are the most abundant, the mitochondrial respiratory cytochromes, enzymes such as catalase