Understanding Sickle Cell Disease: Genetics and Pathophysiology

The middle and posterior cerebral artery territories are affected most commonly, similar to the pattern seen in adults, though the anterior territory can occasionally be involved too. Regular transcranial Doppler screening from two years of age is the key prevention tool: it uses ultrasound to measure blood flow velocity in the cerebral vessels and identifies children at higher risk of stroke early, so that preventive medication and closer monitoring can begin before a stroke actually happens.

In pregnant women who have generally done well and had infrequent pain crises up to childbearing age, hydroxyurea is usually held during pregnancy since it is not a good option for fetal development. Good hydration and avoiding any other stressful conditions are advised instead, and folic acid supplementation must continue.

As early as the disease is detected, sometimes as young as two months of age.

The best outcomes are under 16 years, 16 to 25 is still viable, and beyond 25 the risks rise and require much more detailed pre-transplant workup, including cardiac and kidney function assessment, though age is not always a fixed barrier if organ function is well preserved and the family is fully committed. A full-match sibling transplant typically costs around $24,000 to $25,000, rising for older patients closer to adult body weight, while a half-match or unrelated-donor transplant through a registry costs around $33,000 to $34,000, since registry and donor-related costs are higher even though complications are reduced.

Gene therapy uses the patient's own stem cells rather than a donor, mobilised and collected the same way as for a transplant, then modified in a laboratory using either a viral vector for gene addition or CRISPR-Cas9 editing to correct the underlying genetic change, a process that currently takes around six months. Because the cells being returned are the patient's own, recovery is generally faster than with a donor transplant, but the therapy currently has FDA approval only for patients aged 12 and older, and it remains expensive and not yet widely available outside the US, Europe and a handful of other countries.

A single mutation on chromosome 11, in the HBB gene, shifts one amino acid from glutamine to valine, causing haemoglobin to fold abnormally into haemoglobin S, which distorts red blood cells into a sickle shape.

It is autosomal recessive. Two carrier parents, each with one sickle gene and one normal gene, have a 25% chance with each pregnancy of having a child who inherits both sickle genes and develops the disease.