Sunday, July 25, 2010

Adrenoleukodystrophy (ALD)

My apologies for posting this late. I am battling off a head cold and sleep was more imperative than blogging last night.

Following up on Wednesday's review of Lorenzo's Oil, I thought you might like to know more about the debilitating metabolic disorder affecting the centerpiece of the movie, Lorenzo Michael Murphy Odone.

Adrenoleukodystrophy (ALD) is one of several diseases called leukodystrophies. ALD is an X-linked genetic disorder, and is very rare (1:42000). This means that a woman (xX) has a mutated X chromosome that can be passed on to both daughters and sons with a 50/50 chance each time that they will inherit the mutation. If a daughter (xX) inherits the mutation she most likely has a healthy X chromosome that can compensate for the mutated gene. Some women may have mild symptoms of these disorders but otherwise remain "carriers" in the gene pool. When a son (xY) inherits the mutation, he will have the disorder. [Duchenne Muscular Dystrophy (DMD) and Fragile X Syndrome (FX) have similar inheritance patterns...interesting] This point comes up during Lorenzo's Oil as Lorenzo's mother, Michaela, struggles with the knowledge that her DNA is the root cause of her son's debilitating disease. (More on this Tuesday...)

Perhaps the most devastating aspect of ALD is that symptoms do not manifest until a boy with the disorder reaches the age of 4-10. Until the symptoms appear every aspect of the boy's development will appear typical. At the outset of the disorder behavioral issues may begin to surface - tantrums, sensory disorder, followed by a decrease in visual, auditory, motor and oral functions. Gradually various bodily functions shut down until death occurs, usually within 10 years of the onset of symptoms.

The gene responsible for this mayhem was identified in 1993 (just after the movie came out). It encodes a "transporter protein" that is responsible for moving an enzyme around. Think of this transporter as the bus that the enzyme takes to work. If the bus breaks down the enzyme can't work. The enzyme is responsible for breaking down long chain fatty acids normally found in our diet. If the enzyme can't get to work the long chain fatty acids build up in the bloodstream. Somehow (no one quite knows how) these excess fatty acids then cause damage to the myelin sheath that surrounds the nervous system. Without myelin nerve cells cannot properly conduct the signals that keep all of our systems working.

The movie, Lorenzo's Oil, is about Lorenzo's parents working alongside and sometimes around the medical community to develop an experimental treatment for ALD. Lorenzo's Oil is actually a mixture of two very specific oils (they are components of olive and rape seed oils in the movie) that, together with a diet low in very long chain fatty acids, helps to lower and keep the level of long chain fatty acids low in the blood serum. A large scale clinical trial is underway to investigate the efficacy of this treatment. It seems particularly effective in cases where the patient is asymptomatic or has mild symptoms. If myelin damage has already occurred there is currently no method to repair that damage. Some other potential treatments include bone marrow transplant, stem cell transplants from cord blood, and some drug trials are underway.

You can read more about ALD, Lorenzo Michael Murphy Odone, and myelin here:


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