Talk:Adrenoleukodystrophy

I'd like to suggest that some material be added to this article so that the average person can better understand ALD. The article is technically perfect but it needs to be more user friendly so that the average person can carry away some understanding after reading it. I don't want to edit it myself but I'll make these suggestions for making the article more reader friendly & useful.

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ALD is a condition affecting boys that triggers a build-up of saturated, very long-chain fatty acids in the brain. The myelin sheath, a protective coating on nerve cells that allows electrical impulses to flow normally from cell to cell, is destroyed. These fatty acids can be identified in the blood at birth. The more severe form of ALD causes brain damage that totally disables a boy within two years...

Dr. Hugo W. Moser, director of neurogenetics at the Kennedy Krieger Institute and professor of neurology and pediatrics at Hopkins, began offering "Lorenzo's oil" to patients and began research to see whether it worked. In 1989, he set out to identify infants and toddlers with the genetic defect, finding 89 patients. He gave them the treatment oil in conjunction with moderate low-fat diet. The severe form of the disease was stalled, according to a study in the latest issue of the Archives of Neurology.

As of this year, 66 of the 89 boys remain well. Twenty-one others showed abnormalities on a brain scan and 10 had neurological symptoms. "We've shown it has a preventative effect," said Moser. "It's very exciting."

There is an adult form of ALD that is less severe but quite disabling. It is often mistaken for multiple sclerosis. Both men and women can have the adult form of ALD. ALD affects one in 17,000 people. In the U.S., there are about 12,000 to 16,000 patients with ALD. Half have the severe form.

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I agree that the article needs to be adapted somewhat for the lay readership. I'd like to avoid all the credentials of the authors of the study. Generally, this distracts from the actual findings, as people tend to home in on a scientist's credentials.

Of course Lorenzo's Oil needs mentioning (perhaps even the Phil Collins song). JFW | T@lk 16:52, 12 July 2005 (UTC)

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Would you (or anyone else) mind editing? With any luck at least a few parents will find in a revised article enough useful information to correctly identify the symptoms in their own sons and begin the treatment, saving the affected families from the inevitably tragedy. Knowledge for its own sake isn't enough at Wikepedia, IMO. To that end I think the article's section on symptoms should extended with a plain English explanation of the symptoms, viz. behavioral changes such as abnormal withdrawal or aggression, poor memory, and poor school performance. Other symptoms include visual loss, learning disabilities, seizures, poorly articulated speech, difficulty swallowing, deafness, disturbances of gait and coordination, fatigue, intermittent vomiting, increased skin pigmentation, and progressive dementia. (I updated one reference link and added another, by the way.)

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Can someone explain the relationship (if any exists) between Acyl-CoA and disrupted peroxisome membrane transport protein ABCD1? I've come to understand that ALD patients lack Acyl-CoA function, and have a mutated ALD gene, resulting in irregular ABCD1 function. Is there a well established connection? 209.236.158.250 (talk · contribs)

How strong do you want it? The linkage is strong, but the mechanism is unclear, see Online Mendelian Inheritance in Man (OMIM): 300100. JFW | T@lk 14:21, 13 December 2005 (UTC)

JAMA

This was reviewed in a JAMA update[1]. JFW | T@lk 00:50, 1 January 2006 (UTC)

Females and ALD

I changed the page back from "always male" to "typically male" because there are reports that heterozygotes can show symptoms:

"Not only men are affected: in the early 1980s it was shown that female carriers are at risk for developing neurological deficits as well"[2]

Cocaine

I have removed the references to cocaine which were entirely unsourced and unsupported by medical science. I have also removed the hurtful reference to Lorenzo's death. This surely violates Wiki principles on mention of living people. I hope whoever put it in feels ashamed of themselves for the upset this has caused to his family. He is alive and living in Fairfax Virginia. Edwardlucas 17:52, 21 July 2007 (UTC)

see also [3] as reference for Lorenzo being alive today. Felsir 20:49, 22 July 2007 (UTC)

Discussion of bulk of text

I moved this bulk of text seen below in italics to this place, because it needs discussion before being returned to the main article.

First, I have to say that it seems completely correct, and well written as well. However, it wasn't really merged with the rest of the text of the article, but rather dumped into it. Wikipedia appreciates contributions, but they need to fit the rest of the text too to be more fluent. Besides, such a way of entrying it gives the suspicion that a copyvio has been done. In fact, the text is completely unreferenced. In this case, such a reference is needed, also because this i is a matter which is hard to form a consensus of. You can not by a majority vote decide whether adrenoleukodystrophy might be caused by the plasma membrane becoming more water-soluble or not. In short, a reference is needed, both for the risk of copyvio and for scrutiny of the information itself.

And please, try to merge it with the rest of the article. Almost everything, except that water-solubility effect, is already mentioned in the article. Thank you! Mikael Häggström 10:31, 12 August 2007 (UTC)

Adrenoleukodystrophy (ALD) is a neurodegenerative disorder in which faulty genetic coding results in the disruption of neurological activity and function. ALD is an inborn error of metabolism that is a consequence of a specific peroxisomal enzyme deficiency. An absent protein that functions in the transport of enzymes into peroxisomes adversely affects the hydrolysis of a predominant lipid type. This enzyme serves to catalyze the hydrolysis of very long chains, saturated fatty acids (VLCSFAs). VLCSFAs accumulate in the brain and spinal cord, thereby affecting neural electrical transmission due to myelin sheath degeneration. The inability of action potential conduction and neurotransmitter release results in dementia, loss of voluntary movement, and senses. VLCSFAs relate to 24-26 carbon saturated fatty acid chains. Saturated fatty acids correspond to high low density lipoprotein (LDL) levels, which contribute to increased blood cholesterol and plague development within blood vessel endothelium. Due to VLCSFAs’ straight configuration, these molecules are capable of solubilization and insertion into the lipophilic myelin sheath. Interactions between these entities may instill a water soluble quality upon the myelin, leading to slow degeneration and separation from the neuronal axon. VLCSFA concentrate within the myelin sheath may also initiate immunological response, in which destruction of the myelin may result. Endoplasmic reticulum synthesis of saturated fatty acids involves the linkage of short fatty acid and two carbon unit combinations. VLCSFAs are thereby degraded by means of peroxisomal β oxidation, which entails the removal of two carbon units from the fatty acid. Very long chain fatty acid (VLCFA) CoA synthase is actively involved in catalyzing fatty acid hydrolytic and condensation reactions, therefore serving as an invaluable entity in fatty acid metabolism. In ALD, malfunctional transport proteins, classified within the ATP-binding cassette transport family, fail to properly transport VLCFA-CoA synthase across the peroxisomal plasma membrane, leading to enzymatic deficiency. A single enzyme was discovered to produce both unsaturated fatty acids, as well as VLCSFA. Lorenzo’s Oil employs a combination of unsaturated fatty acids called oleic acid and erucic acid. These macromolecules competitively inhibit the VLCSFA-enzyme association, thereby preventing saturated fatty acid production. Primarily, oleic acid was utilized and found effective in lowering VLCSFA blood levels, but was not sufficient in normalizing these concentrations. Erucic acid served to advance this compound’s pharmacological effect due to a more lengthy composition. ALD is a sex-linked disorder involving the expression of a lethal X-linked recessive allele. A chromosomal mutation codes for a nonfunctional VLCFA-CoA synthase transport protein, leading to defective enzymatic reactivity. The mother lacks the disease due to a present dominant allele that masks the phenotypic activity of the afflicted allele. A father contributes a Y chromosome that lacks the capability to dominate the mother’s abnormal recessive alleles. Lorenzo’s Oil has proven effective in the temporary or complete suppression of ALD, yet requires pre-symptomatic administration. Perhaps, further improvements in medicinal development may promote better treatment and diagnostic testing.

Minor Critique

Under the Symptoms section, one sentence reads: The most severe type is the childhood cerebral form for most likely the male, which normally occurs between the ages of 4 and 10 and is characterized by failure to develop, seizures, ataxia, adrenal insufficiency, as well as degeneration of visual and auditory function.

The sentence is a little oddly worded. Failure to develop what, exactly? It could also be misconstrued as saying the individual who had this disorder has a failure to develop seizures, etc. —Preceding unsigned comment added by 65.67.115.63 (talk) 18:50, 31 May 2008 (UTC)

Done. If it were up to me, I'd replace the section on Lorenzo Odone with one on Hugo Moser. The usefulness of Lorenzo's oil, if any, remains to be proven, which is why studies are still being done. Pustelnik (talk) 01:09, 8 July 2008 (UTC)

Concerns regarding article quality

It must be noted how, despite the profusion of descriptions of mechanisms of action and symptoms, there are very few good sources. I must also call into question the overall quality of the English in this article - especially in a few sections such as this one:

===Cause===

Slowly by stripping the myelin sheath (a protective sheath on your nerves in your brain) :the affected person would slowly begin to loose body function and eventually will not be :able to talk. There is a over load of long chain fatty acids that ones body cannot :dispose of. This does not follow the basic unit of life. (Everything one takes in must :be able to be disposed of as waste) This over load of fatty acids will build up in your :brain and that is what strips the Myelin Sheath.

Note the complete lack of citations where needed, questionable use of English and the direct derivation from the movie Lorenzo's Oil (an unreliable source, to say the least). There are several more examples dotted throughout the article.

Finally, I would like to suggest that the "summary" be split up and merged with the various sections in the body - as is, it is comparable in length of the article itself. --83.183.127.178 (talk) 02:28, 21 November 2011 (UTC)