Day one
Adrenoleukodystrophy
• Called ALD
• a rare, inherited metabolic disorder
• the fatty covering (myelin sheath) on nerve fibers in
the brain is lost, and the adrenal gland degenerates,
leading to progressive neurological disability and
death.
• “Leuko” refers to white color of neuron sheath
• “Dystrophy” refers to abnormal development
• can become active at any point in a boy's life
Symptoms
• Pediatric onset occurs between the ages of 4 and
10 years.
• The boys develop normally until the onset of
symptoms that are often mistaken for attention
deficit disorder.
• There then appear to be signs of serious
neurological involvement including impaired
auditory discrimination, visual disturbances,
impaired coordination, dementia and seizures.
• These symptoms generally progress rapidly and
lead to a vegetative state within two years and
death anytime thereafter.
Day two
Testing
The test for ALD and AMN is a blood test to
determine the levels of very long chain fatty acids
in the blood.
Additionally, known carriers can submit
their children to genetic testing to
determine whether their sons have the gene
for development, or if their daughters are in
fact carriers as well.
The figure above shows the location of the Adrenoleukodystrophy gene
on the x chromosome. It was borrowed from http://www.ncbi.nlm.nih.gov/
disease/chr21-Y.html and modified in MS Paint v98 by the Microsoft Corporation.
The above picture
shows an affected
boy. It was borrowed
from
http://www.mtsu.edu/~
jsanborn/dshp.htm
There are many specific symptoms that lead to the total cognitive and
behavioral impairment. The range of symptoms is:
oAttention deficit disorder
oImpaired vision
oImpaired speech
oImpaired motor function
oCognitive and behavioral impairment
oComa
oSeizures
oSwallowing difficulties
Adrenomyeloneuropathy.
(AMN)
• When the gene becomes active in adulthood
• Men that experience AMN also endure
demyelination, however, it most commonly
restricts itself to the long tracts of the spinal
column causing increasing difficulty with walking,
as well as bladder and bowel disturbances over a
period of decades.
• In approximately thirty-five percent of the men
who develop AMN, demyelination of the brain
does take place, with a much more debilitating
effect.
Up to 40% of the heterozygotes, or women
who are carriers of these disorders,
experience AMN like symptoms as their
lives progress. Adrenal function is almost
always normal.
Adrenoleukodystrophy is an extremely rare disease, affecting only 1:75,000 live male
births.
The disease affects all races equally. There have been no known female sufferers of the
childhood onset form of the disease, so the incidence in girls does not exist.
It is estimated that 1:42,000 females in the United States carries the defective gene that
causes Adrenolekodystrophy.
People with ALD accumulate high levels of saturated, very long chain
fatty acids in their brain and adrenal cortex because the fatty acids are
not broken down by an enzyme in the normal manner.
The ALD gene was discovered in
1993, it was a surprise that the
corresponding protein was in fact a
member of a family of transporter
proteins, not an enzyme.
It is still a mystery as to how the transporter affects the function the fatty
acid enzyme and, for that matter, how high levels of very long chain fatty
acids cause the loss of myelin on nerve fibers.
Lorenzo’s Oil is a mixture of oleic and erucic acids,
that helps to normalize the levels of very long chain
fatty acids in boys with adrenoleukodystrophy.
Having low levels of very long chain fatty acids in the
body will help to slow and minimize the effects of the
disease by preventing them from accumulating in the
body. Unfortunately, use of the oil causes gross
lowering of platelets in patients. Children with this
disorder are deficient in docasahexaenoic acid, and
clinical trials are being conducted with administration
of this acid derived from algae.
The picture shows the
makeup of oleic and
erucic acids and how
they combine to make
"Lorenzo's Oil." It was
borrowed from
http://carbon.cudenver.edu/~bstith/
loren.htm
1) Are they normally present in the body?
YES!
2) What is their function?
They are part of brain membranes, including myelin,
the "insulation" around nerve fibers.
3) Where do they come from?
- Dietary sources
- Elongation of shorter fatty acids in the body
4) What could cause the increase levels of VLCFA
in ALD/AMN?
- Body makes too much
- Body doesn't remove excess amounts
5) Which of these possibilities is correct?
Studies with patient volunteers and in cells in the laboratory
have shown that the process that normally breaks down or
oxidizes VLCFA's is defective in ALD/AMN.
Prognosis for the disease is very poor. The disease
will disable and kill a child by age 14. Advances in
ALD treatment have progressed rapidly over the last
decade and clinical trials being conducted now may
yield a cure in the future. Generally, if the disease is
caught before the child is symptomatic, and aggressive
treatment is used, the progression of the disease may
be substantially slowed or halted. However, unless
there is a family history of the disease, boys are
generally not tested for it and diagnosed before they
have symptoms. Currently, the Myelin Project is
experimenting with ways to regenerate myelin in the
brain and the central nervous system.
Lorenzo’s Oil is a
mixture of oleic and
erucic acids, that
helps to normalize
the levels of very
long chain fatty acids
in boys with
adrenoleukodystroph
y.
The Stop ALD Foundation was started immediately following the
year 2000 ALD diagnosis of Oliver Abraham Lapin – at the time a
sweet, caring, and extremely intelligent 8 year-old boy from
Houston, Texas. Oliver was misdiagnosed for years and, by the
time an accurate diagnosis was made, he was already severely
affected with no treatment available to help him. That diagnosis
did provide early warning for the 2 other affected boys in the
family who could be “saved.” The expression “it takes a village”
was taken to heart when Oliver’s extended family started The
Stop ALD Foundation in early 2001.
On Thursday, August 12, 2004, the day before Oliver’s 12th
birthday, Oliver passed away from complications related to ALD.
He was at home lovingly surrounded by his family.
The Stop ALD Foundation wishes to thank the outpouring of
support and donations that we have received in memory of Oliver.
We will continue on our path and focus to make sure more
children are diagnosed earlier, and that better, more effective,
and safer treatments are available.
We’ll so deeply miss you Oliver. We’ll never, ever forget you.
Ideas for persuasive papers or essays:
If a person knows they are a carrier for a fatal
disease should they have children?
Should they be allowed to manipulate genes (choose the
sex of their child?)
Should stem cell research be used? –from existing cell
lines?
From donors (dead/alive)? –from embryonic tissue from
abortions?
Should government funded research be limited to diseases
which effect large numbers – or should we spend money on
rare diseases?
Is cloning an option as a treatment for disorders?