Chapter 21: Disorders of Haem Metabolism: Iron and the Porphyrias

Disorders of Haem Metabolism: Iron and the Porphyrias details how haem is synthesized from precursors like glycine and succinate, primarily in the bone marrow and liver, where it serves as a vital prosthetic group for oxygen transport in haemoglobin and muscle myoglobin. The text emphasizes iron’s essential yet toxic nature, explaining its transport via transferrin and its storage within ferritin or haemosiderin to maintain systemic homeostasis. Central to the discussion are the mechanisms of iron absorption regulated by the protein hepcidin and the pathological manifestations of iron deficiency, which typically results in microcytic hypochromic anaemia. Conversely, the chapter examines iron overload syndromes, particularly hereditary haemochromatosis driven by HFE gene mutations, which can lead to multisystem organ damage such as cirrhosis, "bronzed" diabetes, and cardiomyopathy. Furthermore, it classifies the porphyrias—a group of rare metabolic disorders arising from specific enzyme deficiencies in the haem biosynthetic chain—into acute varieties presenting with neurovisceral crises (such as abdominal pain and peripheral neuropathy) and cutaneous forms characterized by severe photosensitivity and skin lesions. Accurate diagnosis involves a comprehensive analysis of plasma iron studies, soluble transferrin receptors, and the detection of specific porphyrin precursors in urine, faeces, and blood to differentiate between these complex metabolic conditions.