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Taking Charge of Your Health


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 while 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 this disease.
Currently, there is also no way to predict who will develop which form. In the childhood cerebral type, the affected
children develop normally for the first few years but neurological symptoms typically
begin in early school years. These symptoms may include new onset behavioral problems,
learning disabilities, seizures, vision loss, deafness, loss of speech, and trouble coordinating
movements. In the adrenomyeloneuropathy type, the most
common form, there are both adrenal and neurological problems. It usually begins in early adulthood.
Symptoms may include stiffness, weakness, clumsiness in the limbs, pain in the hands
and feet, muscle spasms, urinary problems, and erectile dysfunction. In the adult cerebral type, men who often
already have AMN symptoms will also start experiencing behavioral changes, memory and
cognitive issues, similar to people with dementia, slurring of speech, and inability to take
care of themselves. In the adrenal insufficiency-only type, there’s
adrenal deficiency but no neurological problems. Symptoms may appear at any time between childhood
and adulthood and include decreased appetite, increased pigment in the skin, low blood pressure,
muscle weakness, and vomiting. While males can develop all forms of this
disease, about half the females who carry the ABCD1 mutation will develop AMN symptoms
typically during middle age. Cerebral forms and adrenal insufficiency are very rare in
females. Now, the diagnosis of adrenoleukodystrophy
may be suspected in people with adrenal insufficiency even in absence of neurological symptoms.
Diagnosis starts with a blood test that measures the amount of VLCFAs. Then genetic testing
is done to confirm the diagnosis. After diagnosis, a brain MRI is done to evaluate the extent
of the disease. Now because adrenoleukodystrophy is caused
by a genetic mutation, there’s no known overall cure, but treatments for the different
forms do exist. For ccALD, it’s important to catch it early with screening because hematopoietic
stem cell transplant, also called bone marrow transplant, can be done, but it’s only effective
if done during the early stages of the disease. Due to this, newborn babies are now being
tested for ALD in several countries and several states in the US. For the adult forms of the
disease, management focuses on treating adrenal insufficiency with supplementation of the
missing steroid hormones. Symptoms like muscle stiffness, pain, and gait problems can be
treated with medications and physical therapy. Alright, as a quick recap, adrenoleukodystrophy,
or ALD, 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. It has variable expressivity, which means that
there are different forms of the disease. The symptoms are neurological or related to
adrenal insufficiency. It’s diagnosed with a blood test that detects VLCFAs levels and
a genetic test. Treatment involves glucocorticoids to counter the adrenal insufficiency, hematopoietic
bone marrow transplantation for the childhood cerebral form, and symptom specific medications
and physical therapy for the adult forms.

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