Wiskott-Aldrich syndrome
Meaning of Wiskott-Aldrich syndrome: One faulty protein leaves blood cells unable to change shape, and three unrelated-looking problems follow from that single defect.
Definition of Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome is a rare inherited immune deficiency carried on the X chromosome, so it appears in boys while their mothers and sisters may carry it without symptoms. Changes in the WAS gene disable a protein that shapes the internal framework of blood cells. Affected boys have too few and abnormally small platelets, persistent eczema, frequent infections, and a raised risk of autoimmune disease.
How is it passed on?
The gene sits on the X chromosome. A boy has one X, inherited from his mother, so a single faulty copy leaves him without any working version. A girl has two, and the healthy copy generally covers for the faulty one, making her a carrier who is usually well. That pattern explains the family picture relatives notice: affected brothers, affected maternal uncles, and unaffected mothers in between. A share of cases arise instead from a new change in the gene, so an inherited condition can still appear with no earlier family history at all.
What does the missing protein normally do?
It works as a switch telling the internal scaffolding of a cell when and where to rebuild itself. Blood cells rely on that constantly. An immune cell crawling through tissue, gripping a target and firing at it is remodeling its own frame every few seconds, and a platelet is pinched off from its parent cell by the same machinery. Without the switch, immune cells respond sluggishly and platelets come out small and are cleared early by the spleen. One defect, several apparently unconnected consequences.
Why do two boys with the same condition differ so much?
| Form | Protein made | Picture |
|---|---|---|
| Classic syndrome | None or almost none | Full triad, autoimmunity, cancer risk |
| X-linked thrombocytopenia | Reduced but present | Low, small platelets and little else |
| X-linked neutropenia | Overactive protein | Shortage of neutrophils, no bleeding tendency |
Two threats grow with age rather than fading. Autoimmune disease, in which the misfiring immune system turns on the body's own blood cells, joints or vessels, affects a large share of those with the classic form. Cancer risk concentrates in non-Hodgkin lymphoma. Replacing the blood-forming cells of the marrow with those of a donor corrects the defect at its source, and this disorder was among the first targets of gene therapy. Older records list it as Aldrich syndrome.
Also known as
Used in a sentence
Wiskott-Aldrich syndrome was confirmed by sequencing of the WAS gene.
Good to know
Platelets in this syndrome are unusually small as well as reduced in number, a combination that distinguishes it from the far commoner immune destruction of platelets of normal size.