Wiskott-Aldrich syndrome
11
October

By Adem Lewis / in , , , , , , , , , , /


Wiskott-Aldrich syndrome is also called eczema-thrombocytopenia-immunodeficiency
syndrome. So, one by one, there’s eczema, also called
atopic dermatitis, which is characterized by dry red patches arising on the skin. There’s a type of thrombocytopenia called
microthrombocytopenia because not only are there very few platelets, but the platelets
are also small in size. And there’s a problem with the immune system
that leads to repeated infections. All of the hematopoietic cells, which are
cells in the bone marrow, produce Wiskott-Aldrich syndrome protein, or WASp for short. There’s also a gene – called the WIPF1 gene,
which encodes a protein called WAS/WASL-interacting protein family member 1, which helps stabilize
Wiskott-Aldrich protein. So WASp, aside from having a really long name
that shortens down to the name of a scary flying insect – helps to reorganize the cell’s
cytoskeleton, and therefore its overall shape. The cytoskeleton can change by either adding
to or removing actin proteins from the end of an actin chain. The chain grows longer in the direction that
a cell wants to move and shortens on the side that a cell wants to move away from. This helps with various cellular activities
like phagocytosis and cellular division. Platelets specifically rely on this functionality,
because they originate from large precursor cells called megakaryocytes. This megakaryocyte has many long arms – like
a squid – and the cytoskeleton changes shape so that these arms can detach to form cellular
fragments called platelets. The platelets then go off to form clots at
damaged sites in the blood vessels, to stop bleeding. Another cell type are the T-cells, which are
a type of immune cell, also rely on the cytoskeleton being able to change shape. When they encounter a pathogen, T-cells form
pseudopods or false legs that reach out and synapse or communicate with other cells. Think of it like they’re shaking hands to
exchange information. Helper T cells get activated when they form
an immunological synapse with antigen presenting cells. And once they’re activated, helper T-cells
activate B-cells which generate antibodies which help destroy the pathogen. Next up are the cytotoxic T-cells and natural
killer cells, which also reorganize their cytoskeleton to form an immunological synapse
with various body cells to do surveillance, and find out if they’re healthy or if they’re
infected or cancerous. If an unhealthy cell is discovered, the immune
cells make that unhealthy cell undergo apoptosis, or programmed cell death. Together, the T-cells, B-cells, and natural
killer cells protect the body from pathogens as well as cancer. There are also T-cells called regulatory T
cells or T-regs, which downregulate the other T cells to limit the immune response and prevent
autoimmune conditions from arising. T-regs also rely on reorganizing their cytoskeleton
to function normally. Finally, there are the phagocytic cells like
monocytes, macrophages, and dendritic cells, which form small foot processes to make their
way towards cytokines. These phagocytic cells are like little bloodhounds
and following a cytokine trail. These cells also perform phagocytosis, to
swallow up debris, dead cells, and bacteria, so that it can be processed and destroyed. In Wiskott-Aldrich syndrome, a mutation in
the gene results in a Wiskott-Aldrich protein that can’t function normally. It’s an X-linked recessive disease, and
as a result, males are affected more often than females. Sometimes, however, the disease isn’t inherited
and instead arises from a spontaneous DNA mutation in the Wiskott-Aldrich syndrome gene. A small mutation in the gene might result
in a mild disease, called X-linked thrombocytopenia, whereas a large mutation can result in a shortened
protein, or no protein at all, and that causes Wiskott-Aldrich syndrome. There’s also a condition called Wiskott-Aldrich
syndrome type 2 which is caused by a mutation in the WIPF1 gene, which is very similar to
Wiskott-Aldrich syndrome. Since the Wiskott-Aldrich protein affects
the cytoskeleton of hematopoietic cells, many cells are affected when a mutation occurs. Megakaryocytes are less able to form platelets,
and the platelets that are made are small and fragile – so it’s called microthrombocytopenia. As a result, individuals can’t form normal
clots and can have excessive bleeding. Helper T-cells and B-cells aren’t able to
form an immunological synapse, resulting in an impaired immune response. For unclear reasons, this leads to an increase
in IgA and IgE antibodies, and normal or decreased levels of IgM and IgG antibodies. T-cells and natural killer cells are also
unable to form normal immunological synapses, which impairs their ability to defend against
pathogens and cancers. Regulatory T-cells are also prevented from
doing their job, making autoimmune diseases more likely. Lastly, phagocytic cells like macrophages
struggle to move around, making it harder for them to clean up debris. The classic triad of symptoms in Wiskott-Aldrich
syndrome includes easy bruising and bleeding, eczema, and recurrent infections. The infections are classically due to encapsulated
bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis,
fungi, such as Pneumocystis jirovecii and Candida albicans, and viruses, such as Molluscum
contagiosum, Varicella zoster virus, and cytomegalovirus. Individuals are also more prone to developing
autoimmune conditions, such as idiopathic thrombocytopenic purpura, and cancers, like
leukemia and lymphoma. The diagnosis is usually suspected based on
the triad of symptoms. The initial workup includes a peripheral smear
which would show thrombocytopenia with small platelets. Flow-cytometry can be used to determine whether
a mutated Wiskott-Aldrich syndrome protein is being produced, though it might not identify
a severely mutated protein. The diagnosis is then confirmed by genetic
sequence analysis of the Wiskott-Aldrich gene. Treatment is mainly aimed at the symptoms
– and includes prophylactic antibiotics, regular intravenous immune globulin infusions, platelet
transfusions in the case of severe bleeding, and potentially surgery to remove the spleen,
which can help to maintain platelet counts within the blood. Immunosuppressive treatment is sometimes needed
to treat autoimmune conditions. Hematopoietic stem cell transplantation is
a potentially curative treatment that is sometimes used. All right, as a quick recap… Wiskott-Aldrich syndrome is a disease of the
immune system that’s genetically inherited in an X-linked recessive manner, so it mostly
affects males. The classic triad of findings include microthrombocytopenia,
repeated infections, and eczema. It’s caused by a mutation of Wiskott-Aldrich
syndrome protein, which is produced by all of the hematopoietic cells. Treatment is focused on controlling the symptoms
and hematopoietic stem cell transplantation is currently the only potentially curative
treatment.


29 thoughts on “Wiskott-Aldrich syndrome

  1. You really need to get to symptoms earlier than halfway through the video. Symptoms, followed by Mechanisms, followed by Prognosis and Treatment.

  2. Hey, your science video explanations are always on point! Simple and easy to understand. However, I find the slides and boards can't standalone as instructional pieces because they are so cluttered and busy (lots of info!) thus making the viewer rely on narration to organize their thoughts. Is there a reason why you purposely do this? Thanks for you contribution to science communication!

  3. There should be osmosis period in medical colleges
    I THINK, In future there will be osmosis online medical college.
    Thanks alot , super easy

  4. Skinny waiter brought pie on small plate without tea and beer.
    Skinny=skin= dermatitis eczema
    Pie= pyogenic infections
    Plates= dec platelet count
    Without tea and beer= DEC T AND B CELL

  5. This channel helped me a lot, recently I have also started my new channel for medical students, I teach only medical topic with the help of diagram which will be easy and students can draw that diagram for their various medical exam to achieve their target goal. 😊☺

  6. Why are infections by encapsulated organisms specifically increased? Is this because some of these patients lack spleens? Or is it an unrelated reason

  7. Thanks a lot by your work. I think thrompocytopenia may be seen on FBC,or CBC, rather than thinbood smear.

  8. i'm patient zero, the very first wiskott carry to have a stem cell transplant in the 90s(cord cells)<*edit*….. as a young boy.
    bruised so bad looked like i was being beat.
    all those books you read about wiskott an stem cell transplants. were wrote off of me…..
    Indiana.
    still have the scar on my chest til this day.
    have to register with the fbi, cause technically, my blood is female.
    there somebody out there who is about 1 year older than me, with the same dna…… o.0
    i wonder if she even knows…………..o.0

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