20. Haemoglobinopathies: disorders of the porphyrin metabolism.

Sickle cell disease

Sickle cell disease is a group of inherited RBC disorders, and the most common intrinsic haemolytic anaemia, i.e. the most common cause of haemolytic anaemia due to intrinsic defects of the RBCs. It’s most common in African and Mediterranean populations.

It’s caused by a point mutation in the beta globin gene causes haemoglobin to precipitate into a sickle-shape when deoxygenized, which gives the name. This leads to microvascular occlusion and haemolysis. There are multiple types with varying severity. The most severe form of sickle cell disease (HbSS) is called sickle cell anaemia.

Diagnosis and evaluation

• Laboratory results corresponding to haemolytic anaemia
• Peripheral blood smear
  • Sickle cells
  • Target cells
  • Howell-Jolly bodies
• Haemoglobin electrophoresis – for confirmation of diagnosis

Thalassaemia

Thalassaemia is a group of diseases characterised by one or more defective globin genes, causing haemolytic anaemia. Like sickle cell anaemia it is more common in Africa and the Mediterranean, but also south-east Asia.

Diagnosis and evaluation

• Laboratory results
  • Corresponding to haemolytic microcytic anaemia
  • RDW normal or ↑
• Peripheral blood smear
  • Target cells
  • Teardrop cells
• Bone marrow biopsy
  • Reactive hyperplasia
• Haemoglobin electrophoresis – to confirm diagnosis
• DNA analysis (PCR) – to confirm diagnosis

Porphyria

Porphyrias are genetic diseases where there are defects in one of the enzymes required for porphyria synthesis. Porphyrins are circular molecules which consist of four porphobilinogen molecules. Many proteins contain porphyrins, including haemoglobin, myoglobin, cytochromes, and NO-activated guanylyl cyclase.

Porphyrias are rare disorders, but the prevalence varies significantly with geography. For example, in Scandinavia, the prevalence is higher. In the US the prevalence of all forms of porphyria is approximately 1:25 000, but in Norway it is approximately 1:5 000.

The most common porphyria worldwide is porphyria cutanea tarda, followed by acute intermittent porphyria and erythropoietic protoporphyria.

Diagnosis and evaluation

Elevated levels of porphyrins and porphyrin precursors in the blood is typical for porphyrias. Porphyrins may also be measured in urine and in faeces. Porphyrins make urine tea-coloured or purple, especially when exposed to sunlight, and these samples must be kept form light before analysis.

Genetic analysis may also be helpful in the diagnosis.