Chediak-Higashi, I-Cell Disease & Kartagener’s Disease

The cytoskeleton is a network of scaffolding that gives cells their shape. The cytoskeleton is made up of intermediate filaments, microtubules, actin, and myosin. Microtubules are cylinders of tubulin that can dynamically assemble and disassemble to change length. Microtubules are very important for multiple types of cellular movement (Mitosis, Axonal Trafficking, Cilia/Flagella…). Motor proteins Dynein and Kinesin travel along microtubules like trains on a track causing these movements. Microtubule functioning is inhibited by drugs like Colchicine (gout), Vincristine (cancer), Paclitaxel (cancer) and Mebendazole (parasites).

 Kartagener’s Syndrome (Primary Ciliary Dyskinesia) is a genetic defect in Dynein motor proteins that prevents proper functioning of the Cilia. Cilia normally beat in a rhythmic wave forcing foreign material out of the body. Immotile cilia in the sinuses, ear, and respiratory tract result in Recurrent Infections (sinusitis, otitis media, pneumonia & bronchitis). Abnormal cilia also lead to Infertility in men (immotile sperm) and women (vaginal mucus builds up and is too thick).

Chediak Higashi is a genetic defect in phagocyte microtubules which fuse the phagosome and lysosome. The defect prevents phagocytes from destroying what they engulf and Giant Granules of undigested material builds up. This causes Recurrent Infection (impaired phagocyte function), Albinism (impaired melanin trafficking) & peripheral neuropathy (impaired axonal transport).

Inclusion Vacuoles I Cell Disease

I-Cell Disease (Inclusion-Cell Disease) is a genetic defect which limits the ability to phosphorylate mannose in the golgi and leads to abnormal cellular trafficking. Mannose-6-Phosphate usually signals newly made enzymes to be delivered to the lysosome. Without this signal these enzymes meant for the lysosome follow the “default” trafficking pathway and are secreted outside of the cell (into the extracellular matrix) damaging other cells. Patients present with lysosomal enzyme deficiencies and the presence of Lysosomal Enzymes Where They Shouldn’t Be (Blood, Urine…). This leads to a wide variety of symptoms such as Abnormal Facial Features, joint problems, and short stature. Additionally, lysosomes cannot function properly in degrading cellular debris which causes accumulation of cellular debris in the lysosome and the formations of inclusions bodies.

 

Now that you are done with this video you should check out the next video in the Biochem section which covers Marfan Syndrome, Osteogensis Imperfecta & Ehlers Danlos.

 

Pictures Used (In order of Appearance)

 

18 thoughts on “Chediak-Higashi, I-Cell Disease & Kartagener’s Disease”

  1. These videos are amazing. I am a very global learner and have managed to get through three years of medical school without gelling into a big picture–these videos are helping me get that big picture as the last month of study closes in. Thank you so much!!

    I’ll hopefully donate something after I’m done with boards. I hope you get to make some for Neuroanatomy/Receptors and Pharmacology.

    Keep up the good work!

    1. Thanks so much for the kind words! I hope to start cranking out a lot more videos this fall as my schedule lightens up a lot during my 4th year rotations

  2. What you’re doing is amazing. Thank you for putting so much into helping others. I was beginning to get frustrated with the amount of study materials when I found you on youtube. I cannot tell you how calm I feel and I know that at the end of it all I’ll have the confidence I need to face the boards knowing I have all the HY’s mastered.
    Thank you so much.
    Look forward to the Pharm HY’s.

    1. Thank you so much for your kind words. Hearing from people like you really makes all of the hard work on this project worth it

  3. These videos are awesome. I just found them as I am about to start my ISP and they are a great review! I hope you keep making them.

    1. thanks for the feedback Amanda! I am definitely planning on making more videos so please check back soon & tell your friends

  4. Hey B-Mac,
    Thanks so much for you VDO’s, so helpful… Just wondering about the HY rating for Kartagener’s syndrome… Im using a couple of USMLE study programs, seems like they barly talk about Kartagener’s, but the other subjects seem to fall in line w your HY rating and how much info and emphasis and questions that are repeating in flashcards and quiz questions. Just wondering your take on this…

  5. Wonderful explanations!!!! You have no idea how awesome it is to have a focus, given the amount of information that is taught to us throughout medical school. Thank you so much for this. Keep it up!!!!!

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