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ATAXIA |
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Ataxia, a
medical term originated from the Greek
language meaning "without order," refers |
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to disturbances in
the control of body posture, motor
coordination, speech control, and eye |
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movements. |
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Several brain
areas, including the cerebellum and the
spinocerebellar tracts, substantia nigra,
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pons, and
cerebral cortex control these functions.
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Injuries in one
or more of these areas or in the spinal cord
may lead to some form of ataxia. |
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Birth trauma,
medication toxicity, drug abuse, infections,
tumors, degenerative disorders, |
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head injury,
stroke, or aneurysm, as well as hereditary
neurological disorders also may cause |
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ataxia. |
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Many different
types of inherited ataxias are presently
known. Examples include Machado- |
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Joseph disease,
ataxia-telangiectasia, and Friedreich ataxia. |
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Description |
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Among children
without inherited neurological disorders,
important causes of ataxia are |
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medication toxicity
and post-infection inflammation of the brain. The
latter may happen as |
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complication of
other viral diseases, such as measles, chicken
pox, or influenza. While most |
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a people recover
completely, some can have permanent neurological
deficits. |
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Accidental ingestion
of some drugs may cause ataxia, seizures, sensory
neuropathies, or |
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coma and death. The
chronic administration of antihistamine medication
and anticonvulsive |
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drugs may cause
ataxia in children, and should not be administered
without instruction of a |
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healthcare provider.
Ingestion of seafood contaminated with high levels
of methyl-mercury |
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also causes ataxia,
as does accidental ingestion of solvents. Some
drugs used in treating |
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certain types of
tumors, such as those in colorectal cancer, are
especially neurotoxic and |
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can induce
temporary, but usually reversible ataxia.
Alcoholism, metabolic disorders, and |
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vitamin deficiencies may also lead to ataxia. |
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Demographics |
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Non-hereditary
ataxia is known as sporadic or acquired ataxia.
Approximately 150,000 people |
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in the United States
alone are presently affected by ataxia, either the
acquired or hereditary |
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form. |
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Friedreich
ataxia is the most common inherited ataxia,
occurring in 1 out of 50,000 population |
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Causes and
symptoms |
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Ataxia may be a
consequence of brain trauma, stroke, or
aneurysm. Chronic and progressive |
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ataxia is generally
associated with either brain tumors or with one of
the several types of |
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inherited
neurodegenerative disorders affecting one or more
brain areas involved in movement
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and coordination
control. Other neurodegenerative disorders, such
as Parkinson's disease and |
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multiple sclerosis,
may present cerebellar and/or gait ataxia as one
of the clinical signs. |
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Another cause of
either chronic or progressive ataxia is the
congenital (present at birth) |
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malformation of some
structures of the central nervous system. |
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Hereditary ataxias
are rare diseases, divided into two main
categories according to the |
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pattern of
inheritance : |
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autosomal dominant
ataxias and autosomal recessive ataxias.
Hereditary ataxias are |
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additionally
classified into types according to the affected
structures and gene location |
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of the defective
chromosome. Autosomal dominant inheritance
requires the presence of |
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the mutation in only
one of the two copies of a gene (maternal or
paternal) to trigger the |
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onset of the disease at
some point in life, whereas autosomal recessive
inheritance requires |
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the inheritance of
the mutation in both maternal & paternal genes.
Other forms of hereditary |
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ataxias are
associated with metabolic disorders, such as the
Maple Syrup Urine Disease, |
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Adrenoleukodystrophy,
and Refsum disease. |
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Autosomal Dominant
Cerebellar Ataxias (ADCAs) are a group of ataxias
divided into Types I, |
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II, and III,
according to the symptoms involved.
Spinocerebellar ataxias (SCAs) Type 1, 2, |
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3, 4, 5, 6, 7, 10, &
11 belong to the ADCA group. Dominant
Spinocerebellar Ataxias (SCAs) |
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have several
overlapping clinical signs, & a common feature
to those belonging to the ADCA |
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group is cerebellar
ataxia, which manifests in difficulty walking and
speaking. SCA1, 2, 3, |
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and 4 may also
involve partial paralysis of the eyes, slow eye
movements, poor motor |
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coordination,
dementia, peripheral neuropathy (pain, numbness,
or tingling sensation in the |
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extremities of limbs
and hands), optic neuropathy, and deafness. All of
these symptoms are |
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not necessarily
present. SCA2 and SCA7 may also result in retinal
damage, whereas those |
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with SCA10 exhibit
loss of muscle control and generalized seizures
without other symptoms. |
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Inherited ataxias |
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SCA1 is
caused by an abnormal gene expression located on
chromosome 6. Genes consist |
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of several different
protein sequences, each coding (providing
instructions) for one specific |
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amino acid. A
sequence error or abnormal repetition of a
nucleotide (a building block of DNA |
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and RNA) in a given
gene impairs adequate protein synthesis or results
in a wrong protein. |
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In SCA1, abnormal
amounts of the nucleotide CAG lead to symptoms
such as eye-muscle |
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dysfunction and
increased tendon reflexes. The onset of symptoms
usually occurs around |
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the age of 30, or
during the fourth decade of life. Increased
amounts of CAG occur in each |
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new generation,
resulting in symptoms that usually appear earlier
in life. SCA1 is also known |
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as Spinocerebellar
Atrophy I, Olivopontocerebellar atrophy I, and
Menzel Type ataxia. |
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SCA2 is
associated with abnormal gene expression on
chromosome 12. Major symptoms |
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include Parkisonism
(tremors and spasticity), myoclonus (muscle
spasms), Pons atrophy, & |
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slowing of eye
movement. SCA2 is subdivided in Episodic Ataxia
Type 1 or EA1 (also named |
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Paroxysmal and
Myokymia syndrome) and Episodic Ataxia Type 2 or
EA2. The onset of EA1 |
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occurs in general
around the five to six years of age, with muscles
quickly becoming flaccid |
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or rigid, tremors in
the head or in the limbs, blurred vision, and/or
vertigo. The severity of |
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these episodes
varies, and episodes usually last for about ten
minutes, although in some |
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cases they may last
for as long as six hours. These episodes are
generally triggered by |
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stressful
situations, anxiety, and abrupt movements, and
also occur spontaneously due to |
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a metabolic
dysfunction. EA2 symptoms usually begin during
school years or adolescence. |
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The crisis starts
with vertigo and ataxia, and is often associated
with involuntary eye |
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movements. |
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This condition is
treatable with daily administration of
acetozolamide. When untreated, |
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crisis may occur a
few times per month, lasting from 1 to 24 hours.
However, most affected |
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individuals will
experience a decrease in intensity and number of
crises as they mature. |
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SCA3 ataxia
is also known as Machado-Joseph disease and the
gene affected is on chromosome 14.
Dystonia (spasticity or |
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involuntary and
repetitive movements) or gait ataxia is usually
the initial symptom in children. Gait ataxia is
characterized by |
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unstable walk and standing, which
slowly progresses with the appearance of some of
the other symptoms, such as abnormal |
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hand movements, involuntary eye movements (i.e., nystagmus), muscular
wasting of hands, and loss of muscle tone in the
face. |
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SCA3 symptoms
greatly vary among affected individuals
as does the age of onset. Higher numbers of the
CAG nucleotide repeats |
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is associated with
earlier onset and more severe symptoms. In
addition, the number of CAG repeats tends to
increase in each new |
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generation, causing
earlier onset and increased severity. There is no
cure for Machado-Joseph disease. |
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SCA4 ataxia's
genetic defect is located on chromosome 16, and
results in major symptoms of cerebellar ataxia and
sensory |
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abnormalities. SCA4
may occur in two different forms, type I or type
III. Both forms present symptoms 5–7 years earlier
per |
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generation. Symptoms
usually become evident in type 1 from ages 19 to
59 years; from 45 to 72 years in type III.
Difficulty |
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walking, loss of
muscle control, loss of fine-movement coordination
of hands, and absence of tendon reflexes are the
main |
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symptoms observed in
this progressive and crippling condition. |
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SCA5 ataxia
is an extremely rare disorder linked to a defect
on chromosome 11. Symptoms include mild ataxia &
speech disorders. |
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SCA5 ataxia was
identified in one family descending from the
paternal grandparents of Abraham Lincoln. |
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SCA6 ataxia
is caused by a mutation on at chromosome 19.
Clinical signs are varied, with some patients
having limb and gait ataxia |
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along with episodic
headaches or nausea, and others having gait
ataxia, speech difficulty, and abnormal eye
movements. Initially, |
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most patients only
sense a momentary imbalance and mild vertigo when
they make a quick movement or turn. After months
or years, |
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balance problems
become more pronounced. The disease progresses
over 20–30 years and eventually leads to severe
disability. |
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The age of onset
ranges from 6 to 86 years. Periodic episodes of
paralysis occur on one side of the body and last
for days. |
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Episodes may be
triggered by head injuries & emotional stress.
Some persons with SCA6 ataxia experience a more
rapid progression |
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and require
wheelchair for support and mobility approximately
5 years after onset. |
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SCA7 ataxia
is also known as olivopontocerebellar atrophy III,
and results from a defect on chromosome 3.
Symptoms of SCA7 |
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ataxia occur earlier
with each generation, and earlier onsets are
associated with more severe symptoms. The onset of
symptoms |
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occurs in younger
ages when the mutated copy of the gene is
inherited from the paternal side. Ataxia, severe
eye problems |
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(retinal and macular
degeneration), and early blue-yellow color
blindness are typical clinical signs of the
disease. Decreased vision |
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occurs in over 80%
of individuals with SCA7 ataxia, and almost one
third of these persons eventually become blind.
Hearing loss is |
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also associated with
SCA7 ataxia, and may slowly progress over decades.
In more severe cases, usually associated with
paternal |
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inheritance of the
defective gene, heart failure, liver disorders,
muscle loss, and developmental delays can all
occur. The degree |
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of severity of SCA7
ataxia, the age of onset, and the rate of
progression greatly vary both within and among
families. |
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SCA10 ataxia
is caused by an unstable protein repeat on
chromosome 22. The main characteristics of SCA10
are generalized motor |
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seizures, irregular
eye movements, gait and limb ataxia, and speech
difficulties. The age of onset ranges from 10 to
40 years. |
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SCA11 ataxia
is a very rare disease, mapped to chromosome 15.
SCA11 progresses slowly over decades, with onset
between |
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adolescence and
young adulthood. All individuals develop gait
disorders, increased reflex action, eye
disturbances and irregular |
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movements, and
speech difficulties. |
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Some inherited
metabolic disorders cause progressive nerve
degeneration with ataxia as one of its symptoms,
as is the case with |
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the group of
diseases known as leukodistrophies. One famous
example is Adrenoleukodystrophy (ALD), a
rare autosomal dominant |
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disease that causes
progressive loss of the myelin sheath that covers
the nerve fibers, along with progressive adrenal
gland |
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degeneration. ADL
has two forms: the X-linked ADL (or X-ADL) and the
non X-linked ADL (or ADL). The X-ADL is the more |
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devastating form of
the disease, with the onset of symptoms occurring
between four and ten years of age. ADL (non
X-linked) |
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disease usually
begins during adulthood, between 21 and 35 years
of age and progresses slowly. In both forms of ADL,
the loss |
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of myelin by nerve
fibers is due to an abnormal accumulation of
saturated long fatty acid chains in the brain,
because of a metabolic |
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error involving a
protein that transports fatty acids. The gene
responsible for X-ADL was identified in 1993. The
disorder was |
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presented in the
film Lorenzo's Oil, based on the story of Lorenzo
Odone and his parents' quest to find a cure for
the disease. |
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Other X-ADL
symptoms are seizures, speech and swallowing
difficulties, gait and coordination ataxia,
visual loss, progressive |
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dementia, & loss
of hearing that ends in deafness. As the
mutation is inherited in the X chromosome, ADL
is more severe in boys |
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than in girls,
because females have two X chromosomes, and
the normal copy (or allele) of the affected
gene will compensate for |
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the
dysfunctional one. Treatment with adrenal
hormones can save the child's life and
Lorenzo's oil, a mixture of oleic and euric |
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acids, reduces
or delays the onset of symptoms in carriers of
the mutation without manifested symptoms. Oral
intake of DHA |
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(docosahexanoic
acid) is prescribed for children and infants
with X-ADL. As the neurological degeneration
is progressive, prognosis |
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is usually poor
with patients dying within 10 years from the
onset of symptoms. |
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Another
metabolic disorder causing ataxia is the maple
syrup urine disease or MSUD, an
inherited disease caused by a metabolic |
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disorder
involving the breakdown of certain amino acids
by enzymes. MSUD may occur in three different
forms: neonatal convulsive |
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crisis
(classical form); progressive mental
retardation (intermediary form); or recurrent
ataxia & encephalopathy (intermittent form). |
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The disease was
first discovered in the Mennonite Community of
Lancaster, PA, where MSUD affects 1 out of 176
individuals, |
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although it is
rare in other populations. MSUD onset may
occur between five months of age and the
second year of life. During |
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crisis, the
urine presents an odor similar to maple syrup
and the blood shows high levels of branched
amino acids and ketoacids. |
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Between crises,
such concentrations are normal both in urine
and blood. Severe crises with high
concentrations of ketoacids |
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may be life
threatening, requiring dialysis. The standard
treatment is protein restriction in the diet;
but some patients who respond |
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to the
administration of thiamine during crises may
benefit from the intake of thiamine on a daily
basis. |
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Refsum
disease is caused by a dysfunction in the
metabolism of lipids that leads to high
concentrations of phytanic acid in tissues |
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and blood
plasma. Phytanic acid is a component of
chlorophyll, obtained through the diet. The
enzyme phytanic acid hydrolase |
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normally helps
eliminate phytanic acid from the body. The
inheritance is autosomal recessive, and the
onset may occur between the |
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first and the
third decade of life. One of the first
symptoms is night blindness, but the pace of
progression varies among affected |
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individuals.
Other main symptoms are irregularities in the
retina of the eye, bone and skin changes, and
the abnormal gait, speech |
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patterns, and
muscle movements associated with cerebellar
ataxia. Treatment involves dietary
restrictions and blood transfusion |
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exchanges aimed
at halting the progression of the disease and
resolving symptoms. |
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Friedreich
ataxia is the most common form of
hereditary ataxia, affecting 1 out of 50,000
individuals. Friedreich ataxia is a |
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progressive
disorder affecting the arms and legs, with
progressive weakness, loss of deep tendon
reflexes, and sensory loss. |
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Diabetes and/or
some forms of heart disease may also be
present in people with Friedreich ataxia.
Onset of symptoms usually |
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occurs before 20
years of age. As symptoms of Friedreich ataxia
are similar to those found in other juvenile
ataxias, diagnosis |
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requires genetic
testing to conform. |
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