Adrenoleukodystrophy (NORD)

40,980views

00:00 / 00:00

Flashcards

Adrenoleukodystrophy (NORD)

of complete

Questions

USMLE® Step 1 style questions USMLE

of complete

A 24-year old man presents to his primary care physician’s clinic due to increasing weakness in his legs for the last three years. He notes that his legs feel very stiff. He reports that he had a maternal uncle with similar issues. On physical exam, the patient has decreased vibratory sensation in the bilateral lower extremities. He exhibits signs of early male pattern baldness. The physician confirms the suspected diagnosis via testing the patient’s plasma for accumulated very-long-chain fatty acids (VLCFA) and a mutation in the ABCD1 gene. Which of the following organelles is affected in this patient’s disease?  

Memory Anchors and Partner Content

External References

First Aid

2024

2023

2022

2021

Adrenal insufficiency p. 353

adrenoleukodystrophy p. 45

Adrenoleukodystrophy p. 46, 538

External Links

Transcript

Watch video only

With adrenoleukodystrophy, sometimes called ALD, adreno- refers to the adrenal glands, while -leuko-, means white, and -dystrophy refers to tissue degradation. So, adrenoleukodystrophy is a rare genetic condition, caused by a mutation in the ABCD1 gene, located in the X-chromosome, that leads to the progressive loss of white matter in the nervous system, and the degradation of adrenal glands. Generally, genes tell our bodies how to make proteins. In this case, the ABCD1 gene directs the body to produce adrenoleukodystrophy protein or ALD protein. ALD protein is a transporter that is found embedded in the membranes of vesicles found in cells that break down specific forms of fatty acids, called peroxisomes. Its function is to import into peroxisomes, a group of fats, naturally present in the human body and in our diets, called very long-chain fatty acids or VLCFAs.

Once inside the peroxisomes, these molecules are broken down into shorter forms of fatty acids. Now, in adrenoleukodystrophy, there’s a mutation in the ABCD1 gene which leads to a defective ALD protein. Without a working ALD protein, VLCFAs have no way of entering the peroxisomes to be broken down, so they accumulate inside cells. This build up of VLCFAs is thought to be damaging to our nerve cells and the glial cells that support them, the cells in our adrenal glands that produce steroid hormones, the cells in the testicles, and some of our immune cells. Adrenoleukodystrophy is inherited in an X-linked fashion. This means that the ABCD1 gene is found on the X-chromosome. Males who carry a ABCD1 gene mutation on their X chromosome will have the condition. 85% of females who carry a ABCD1 gene mutation on one of their X chromosomes present higher levels of VLCFAs and half experience symptoms.

Now, adrenoleukodystrophy has variable expressivity, which means that the symptoms between each person with the condition can differ greatly, even within the same family. For this reason, an affected person can develop four main types of adrenoleukodystrophy. The four main types are the childhood cerebral type, called ccALD, the adult cerebral type, called acALD, the adrenomyeloneuropathy or AMN type, and adrenal insufficiency-only type. It’s important to note that in the cerebral forms of ALD, there is a rapidly progressive inflammation of the brain resulting in destruction of the brain’s white matter, the AMN type is due to a slowly progressive degeneration of the long nerve fibers in the spinal cord and the peripheral nerves. Despite extensive research it remains unknown why some people develop one versus the other form of the disease. Currently, there is also no way to predict who will develop which form.

Elsevier

Copyright © 2024 Elsevier, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Cookies are used by this site.

USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME). COMLEX-USA® is a registered trademark of The National Board of Osteopathic Medical Examiners, Inc. NCLEX-RN® is a registered trademark of the National Council of State Boards of Nursing, Inc. Test names and other trademarks are the property of the respective trademark holders. None of the trademark holders are endorsed by nor affiliated with Osmosis or this website.

RELX