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Wiskott-Aldrich syndrome

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High Yield Notes

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Flashcards

Wiskott-Aldrich syndrome

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Questions

USMLE® Step 1 style questions USMLE

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A 2-year-old boy is brought to his primary pediatrician for evaluation of recurrent infections. The parents report the patient had two episodes of severe pneumonia, an episode of otitis media, and herpes labialis in the past nine months. He was born at 38 weeks gestation to a 28-year-old otherwise healthy woman. He eats and drinks normally and has achieved the normal developmental milestones. Vitals are within normal limits. Physical examination demonstrates a well-developed and well-nourished child with fair complexion. He has eczema on his cheeks and trunk as well as petechiae on the bilateral lower extremities. Laboratory evaluation reveals a leukocyte count of 8,000/mm3 and a platelet count of 70,000/mm3. Flow cytometry of peripheral lymphocytes reveal absence of the WAS protein. Which of the following immunologic processes is most likely affected given this patient's findings?

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Eczema

Wiskott-Aldrich syndrome p. 115, 726

Thrombocytopenia p. 413

Wiskott-Aldrich syndrome p. 115

Wiskott-Aldrich syndrome p. 115

labs/findings p. 726

X-linked recessive disorder p. 59

X-linked recessive disorders

Wiskott-Aldrich syndrome p. 115

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Transcript

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Content Reviewers

Rishi Desai, MD, MPH,Yifan Xiao, MD

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.

Summary

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder that primarily affects males. The condition is caused by mutations in the WAS gene, which encodes for the Wiskott-Aldrich syndrome protein (WASP). The signs and symptoms of Wiskott-Aldrich syndrome can vary widely, but often include recurrent infections due to a weakened immune system, eczema, easy bruising or bleeding due to decreased platelets and abnormal clotting, autoimmune disorders such as rheumatoid arthritis or autoimmune hemolytic anemia, and increased risk of developing certain types of cancer, including lymphoma and leukemia.

Sources

  1. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  2. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  3. "Yen & Jaffe's Reproductive Endocrinology" Saunders W.B. (2018)
  4. "Bates' Guide to Physical Examination and History Taking" LWW (2016)
  5. "Robbins Basic Pathology" Elsevier (2017)
  6. "Membrane grease eases platelet maturation" Blood (2015)
  7. "Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation" Blood (2004)
  8. "Clinical course of patients with WASP gene mutations" Blood (2004)