FRIEDREICH'S ATAXIA (freed'rikes at'aksy'uh)
nb. italics are used to explain or expand clinical description
This is a clinical
description, which I have edited, and reformatted. I have added the Italic notes, and
the footnote. Friedreich's Ataxia encompasses variations due to individual responses to
the key disease effects. These effects are noted below and are common to all sufferers, although the intensities and chronology is widely variable,
DEFINITION:
A multisystem disorder characterized by progressive ataxia and neurological, cardiac,
musculoskeletal, and endocrine manifestations.
EPIDEMIOLOGY
- incidence: 1/100,000 live births (average Caucasian)
Canada 1/37,000, US 1/50,000, Italy 1/22,000, Japan below 1/1,000,000, Africa ~ unknown
- age of onset: usually prior to 10 years of age (but as late as 16 years)
- risk factors: familial - autosomal recessive
- chrom.#: 9q13-q21.1
- gene: frataxin
clinical features similar in members of same family
by chronology of symptoms but not necessarily by rate of progression
heterozygotes are phenotypically normal
this is a fancy way of saying the gene behaves in a typical single gene recessive
manner, ie. 1 in 4 offspring of carriers etc.
PATHOGENESIS: nb. read '->' as 'leading to..'
genetic defect -> impaired expression of frataxin -> accumulation of iron within the
mitochondria of affected cells -> production of free radicals within the affected cells
-> cell death -> phenotypic expression in the nervous system (CNS and peripheral nerves), cardiac tissue and pancreas
phenotypic indicates that the effect is identical between sufferers at least at cell
level, although the effects at individual level are often quite diverse
CLINICAL FEATURES:
- Neurological Manifestations
- Ataxia (unsteadiness)
initial presentation in 95% of cases slowly progressive -> loss of ambulation within
20 yrs
- Cerebellar Dysfunction
- dysarthria (explosive) - speech becomes hard to synchronize
- dysdiadokokinesia - fast or complex motion difficult
- finger-nose ataxia - next doctor who asks this, I'll poke HIS eyes!
- Dysfunctions more common & severe in the lower limbs than upper limbs
- head titubation - head wobble
- ocular dysmetria - the doctor moves a finger before the subject eyes and
observes the eye movement. Dysmetria is overshooting, misdirection, and wobbling
of gaze direction, causing Nystagmus, double vision, and wandering focus. (and
all BEFORE you hit the scotch!)
- positive Romberg test - while still able to stand, get subject to stand,
legs together, then close eyes. the positive result refers to sight balance
remaining whilst ear balance has failed. ie. closey eyes, fally over.
- Reflexes absent - deep tendon reflexes - extensor plantar reflex
note here that since a gene test has been in use, some people with hyper
reflexes have been re-classified as FARR Friedreich's ataxia with retained
reflexes. Hyper reflexes also occur in many SCAs (spinocerebellar ataxias)
- Sensation
- loss of vibration and position sense
- impaired light touch and pain sensation - variable between none and hyper on
same subject, ie. most of us suffer cuts unnoticed, but can't tolerate a lentil in
a shoe. I ripped a toenail off, and did not notice
- Others
- normal intelligence
- neurosensory hearing loss - cannot separate voices from background sounds,
for example
- muscle weakness in hands and feet - inability to determine pressure, I have
watched a pen fall from my fingers in disbelief whilst my perception was that I
had it gripped
- Cardiac Manifestations
Hypertrophic Cardiomyopathy (in 90% of patients)
- systolic ejection murmur - you need a doctor with a stethoscope for this one
(or a nurse with black stockings!)
- SOBOE, palpitations, chest pain (angina), arrhythmias, congestive heart failure,
death
SOBOE = Shortness Of Breath On Exertion.
Congestive heart failure and Sudden Cardiac death are the major cause of death in FA.
The usually quoted average life span is 37 with most deaths in the teens and early
twenties who account for around half FA deaths
Musculoskeletal Manifestations
- hammer toes
- pes cavus (high-arched feet)
- progressive kyphoscoliosis - hunch back which can affect breathing
my speculation is that all of these, and the cardiomyopathy are the result of
inability to relax muscles, which shorten, and cause bad heart function, walking
on toes (heels off ground) curled fingers etc.
Please comment on this hypothesis
Endocrine Manifestations
- insulin dependent diabetes mellitus
- onset in 3rd decade in 10-20% of patients
INVESTIGATIONS:
- Evoked Potentials
abnormal auditory brainstem, spinal somatosensory, visual evoked potentials
- EMG
slowed nerve conduction velocities in affected limbs
- ECG
reduced T wave amplitude, RVH and/or LVH, arrhythmias
- Imaging Studies
x-rays to follow musculoskeletal manifestations
- Serum
abnormal glucose tolerance test, hyperglycemia
MANAGEMENT:
- Supportive
- no treatment available to stop progression of disease
- symptomatic treatment of various manifestations
*********************************************
The above is a definitive overview of FA and includes both early and late symptoms,
most of which an FAer will suffer sooner or later. Personally I don't yet have diabetes,
nor kyphoscoliosis. Also my eyesight is fine, but my arms are getting too short to read
a book! Most of the rest I have to some degree. I have used a wheelchair since about
1985 and indoors since 1991 about when I stopped driving. My last nine years driving
was with hand controls. I could not carry a cup of drink unspilt from 1970 diagnosed
1978 at first visit to 'neuro' (a very rare result apparently!) But still had the tests
to confirm. It is an easy diagnosis, but very few doctors are aware of it. There is a
gene test now, but the symptoms above are easily checked and the seven Neurological
symptoms define it distinctly, although they may not all appear at first, but are usually
present before 16 years of age. The lack of reflexes tends to be our first symptom.
(except those with FARR)
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