Machado-Joseph disease

Infobox_Disease
Name = Machado-Joseph disease


Caption =
DiseasesDB = 31961
ICD10 = ICD10|G|11|1|g|10
ICD9 = ICD9|334.2
ICDO =
OMIM = 109150
MedlinePlus =
eMedicineSubj =
eMedicineTopic =
MeshID = D017827

Machado-Joseph disease (or Spinocerebellar ataxia type 3) is a type of spinocerebellar ataxia that causes ophthalmoplegia and mixed sensory and cerebellar ataxia.

Based on DNA studies, MJD is the most widespread, autosomal dominant inherited form of ataxia in the world. Fact|date=September 2008

Causes

Chromosome 14 is where the gene that is responsible for MJD is located.

It is caused by a mutation in the ATXN3 gene.

History

It was first identified in 1972. [cite journal |author=Nakano KK, Dawson DM, Spence A |title=Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts |journal=Neurology |volume=22 |issue=1 |pages=49–55 |year=1972 |pmid=5061839 |doi=]

Unlike many other medical conditions, Machado-Joseph disease isn't named after researchers. It is named after two men ("William Machado" and "Antone Joseph") who were the patriarchs of the families in which the condition was initially described.cite web |url=http://www.ataxiacenter.umn.edu/ataxia/aboutataxia/hereditary/sca3/home.html |title=SCA-3 - Ataxia Center in the Medical School at the University of Minnesota |format= |work= |accessdate=]

ymptoms

Symptoms of MJD are memory deficits,cite journal |author=Kawai Y, Takeda A, Abe Y, Washimi Y, Tanaka F, Sobue G |title=Cognitive impairments in Machado-Joseph disease |journal=Arch. Neurol. |volume=61 |issue=11 |pages=1757–60 |year=2004 |month=November |pmid=15534186 |doi=10.1001/archneur.61.11.1757 |url=http://archneur.ama-assn.org/cgi/pmidlookup?view=long&pmid=15534186] spasticity, difficulty with speech and swallowing, weakness in arms and legs, clumsiness, frequent urination and involuntary eye movements. Symptoms can begin in early adolescence and they get worse over time.

Treatment

There is no cure for Machado-Joseph Disease, however, there are treatments available for some symptoms. For example, spasticity can be reduced with Antispasmodic drugs, such as baclofen. Eventually, MJD leads to paralysis however, intellectual functions usually remain the same.

Prognosis

Life expectancy ranges with people who have the disease. A normal life expectancy is expected in patients with a mild form of MJD. Those with severe forms of MJD are expected to live only to their mid-thirties. The cause of death of those who die early is often aspiration pneumonia.

Pathophysiology

MJD has lengthy irregular repetition of the DNA genetic code located within a gene on chromosome 14q. The code "CAG" is repeated and produces a mutated protein called ataxin-3. (Normally, the number of copies is between 13 and 41.)cite journal |author=Lima M, Costa MC, Montiel R, "et al" |title=Population genetics of wild-type CAG repeats in the Machado-Joseph disease gene in Portugal |journal=Hum. Hered. |volume=60 |issue=3 |pages=156–63 |year=2005 |pmid=16340213 |doi=10.1159/000090035 |url=http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=HHE2005060003156]

The pons (a structure located on the brain stem) is one of the afected areas by MJD. The striatum (a brain area connected to balance and movement) is also affected by this disease, which could explain both of the main motor problems cause by MJD: the tightening and twisting of the limb and the abrupt, irregular movements. [http://www.cienciahoje.pt/index.php?oid=26002&op=all]

In affected cells, this protein piles up and assembles intranuclear inclusion bodies.

These insoluble spheres are located in the nucleus of the cell. These spheres conflict with the normal activity of the nucleus and induce the cell to degenerate and die.

Classification

The types of MJD are characterized by the onset and age and range of symptoms.

* Type I is distinguished by arrival between the ages of 10 and 30 years of age. It usually has fast development and severe rigidity and dystonia.

* Type II typically begins between 20 and 50 years of age. It has an intermediate progression and causes symptoms that include spasticity, exaggerated reflex responses and spastic gait.

* Type III MJD has a slow progression. Symptoms include muscle twitching, tingling, cramps, unpleasant sensations such as numbness, pain in the feet, hands and limbs and muscle atrophy. Patients typically have an onset between the ages of 40 and 70. Nearly all patients experience a decline in their vision such as blurred vision, double vision, inability to control eye movements, and loss of capability to distinguish color. Some patients also experience Parkinson’s-like symptoms.

Diagnosis

MJD can be diagnosed by recognizing the symptoms of the disease and by taking a family history. Physicians ask patients questions about the kind of symptoms relatives with the disease had, the progression and harshness of symptoms, and the ages of onset in family members.

Presymptomatic diagnosis of MJD can be made with a genetic test.cite journal |author=Maciel P, Costa MC, Ferro A, "et al" |title=Improvement in the molecular diagnosis of Machado-Joseph disease |journal=Arch. Neurol. |volume=58 |issue=11 |pages=1821–7 |year=2001 |month=November |pmid=11708990 |doi= |url=http://archneur.ama-assn.org/cgi/pmidlookup?view=long&pmid=11708990]

Ethical Consideration

Ethicists have used Machado-Joseph disease as a paradignamtic illness to discuss the rights of a community of patients to control "ownership" of their disease, particularly when it comes to research on genetic testing.cite journal |author=Appel J, Friedman JH |title=Genetic markers and the majority's right not to know |journal=Mov. Disord. |volume=19 |issue=1 |pages=113–4 |year=2004 |month=January |pmid=14743372 |doi=10.1002/mds.20014 |url=http://dx.doi.org/10.1002/mds.20014]

References

External links

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* [http://health.enotes.com/neurological-disorders-encyclopedia/machado-joseph-disease eNotes]
*dmoz|Health/Conditions_and_Diseases/Genetic_Disorders/Machado-Joseph/