Adrenoleukodystrophy
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Adrenoleukodystrophy (ALD) is one of a
group of genetic disorders called the
leukodystrophies that
cause damage to the myelin sheath, an insulating membrane that
surrounds nerve cells in the brain. People with ALD accumulate high
levels of saturated, very long chain fatty acids (VLCFA) in the
brain and adrenal cortex because they do not produce the enzyme that
breaks down these fatty acids in the normal manner. The loss of
myelin and the progressive dysfunction of the adrenal gland are the
primary characteristics of ALD. ALD has two subtypes. The most
common is the
X-linked form (X-ALD), which involves
an abnormal gene located on the X-chromosome. Women have two
X-chromosomes and are the carriers of the disease, but since men
only have one X-chromosome and lack the protective effect of the
extra X-chromosome, they are more severely affected. Onset of X-ALD
can occur in childhood or in adulthood. The childhood form is the
most severe, with onset between ages 4 and 10. The most common
symptoms are usually 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. In
the milder
adult-onset form, which typically begins
between ages 21 and 35, symptoms may include progressive stiffness,
weakness or paralysis of the lower limbs, and ataxia. Although
adult-onset ALD progresses more slowly than the classic childhood
form, it can also result in deterioration of brain function. The
abnormal genes that cause
neonatal ALD are not
located on the X-chromosome, which means that both male and female
babies can be affected. Symptoms include mental retardation, facial
abnormalities, seizures, retinal degeneration, weak muscle tone,
enlarged liver, and adrenal dysfunction. This form usually
progresses rapidly. A
mild form of ALD is
occasionally seen in women who are carriers of the disorder.
Symptoms include progressive stiffness, weakness or paralysis of the
lower limbs, ataxia, excessive muscle tone, mild peripheral
neuropathy, and urinary problems.
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Adrenal function must be tested periodically in
all patients with ALD. Treatment with adrenal hormones can be
lifesaving. Symptomatic and supportive treatments for ALD include
physical therapy, psychological support, and special education.
Recent evidence suggests that a mixture of oleic acid and euric
acid, known as “Lorenzo’s Oil,” administered to boys with X-ALD can
reduce or delay the appearance of symptoms. Bone marrow transplants
can provide long-term benefit to boys who have early evidence of
X-ALD, but the procedure carries risk of mortality and morbidity and
is not recommended for those whose symptoms are already severe or
who have the adult-onset or neonatal forms. Oral administration of
docosahexanoic acid (DHA) may help infants and children with
neonatal ALD.
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Prognosis for patients with ALD is generally poor
due to progressive neurological deterioration. Death usually occurs
within 1 to 10 years after the onset of symptoms.
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The NINDS supports research on genetic disorders such
as ALD. The aim of this research is to find ways to prevent, treat,
and cure these disorders. Intensive basic research has proposed
two
new approaches, 4-phenylbutyrate and lovastatin, which could
potentially lower levels of VLCFA in the brain. Therapeutic trials
for both agents are planned.
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National Organization for Rare Disorders (NORD)
National Tay-Sachs and Allied Diseases Association
United Leukodystrophy Foundation
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