Machado-Joseph disease

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Machado-Joseph disease
Classification and external resources
ICD-10	G11.1
ICD-9	334.2
OMIM	109150
DiseasesDB	31961
MeSH	D017827

Machado-Joseph disease or Spinocerebellar ataxia type 3 is an extremely rare hereditary ataxia, which means a lack of muscle control. It is caused by a certain mutation that results in degeneration of cells in the hindbrain.^[1] Some symptoms, such as clumsiness and rigidity, make MJD commonly mistaken for drunkenness and/or Parkinson's disease.

Machado-Joseph disease is a type of spinocerebellar ataxia that causes ophthalmoplegia and mixed sensory and cerebellar ataxia.

Contents 1 History 2 Symptoms 3 Treatment 4 Prognosis 5 Pathophysiology 6 Classification 7 Diagnosis 8 Ethical Consideration 9 References 10 External links

[edit] History

The disease was first identified in 1972.^[2]

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.^[3]

[edit] Symptoms

Symptoms of MJD are memory deficits,^[4] 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.

[edit] 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. The Parkinsonian symptoms can be treated with levodopa therapy. Prism glasses can reduce diplopic symptoms. Physiotherapy can help patients deal with disability due to gait problems. Walkers and wheelchairs can greatly help the patient with everyday tasks. Eventually, MJD leads to paralysis however, intellectual functions usually remain the same.

[edit] 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.

[edit] Pathophysiology

The disease is caused by a mutation in the ATXN3 gene, which is located on chromosome 14q. The gene contains lengthy irregular repetitions of the code "CAG", producing a mutated protein called ataxin-3. (Normally, the number of copies is between 13 and 41.)^[5] MJD is an autosomal dominant disease, meaning that if either parent gives the defective gene to a child, the child will show symptoms of the disease.

The pons (a structure located on the brain stem) is one of the areas affected 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.^[6]

In affected cells, this protein builds 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.

[edit] 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 Parkinsonian symptoms.

[edit] 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.^[7]

[edit] Ethical Consideration

Ethicists have used Machado-Joseph disease as a paradigmatic 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.^[8]

[edit] References

[edit] External links

• -234487767 at GPnotebook
• machado_joseph at NINDS
• eNotes
• Machado-Joseph disease at the Open Directory Project

v • d • e Pathology of the nervous system, primarily CNS (G04–G47, 323–349) Inflammation Brain Encephalitis (Viral encephalitis, Herpesviral encephalitis) · Cavernous sinus thrombosis · Brain abscess (Amoebic) Spinal cord Myelitis: Poliomyelitis · Demyelinating disease (Transverse myelitis) · Tropical spastic paraparesis Both/either Encephalomyelitis (Acute disseminated) Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders Basal ganglia disease: Parkinsonism (PD, Postencephalitic, NMS) · PKAN · Tauopathy (PSP) · Striatonigral degeneration · Hemiballismus · HD · OA Dyskinesia: Dystonia (Spasmodic torticollis, Meige's, Blepharospasm) · Chorea (Choreoathetosis) · Myoclonus (Myoclonic epilepsy) Tremor (Essential tremor, Intention tremor) · Restless legs · Stiff person Dementia Tauopathy: Alzheimer's (Early-onset) · Frontotemporal dementia/Frontotemporal lobar degeneration (Pick's, Dementia with Lewy bodies) Multi-infarct dementia Mitochondrial disease Leigh's Demyelinating autoimmune (Multiple sclerosis, Neuromyelitis optica, Schilder's disease) · hereditary (Adrenoleukodystrophy, Alexander, Canavan, Krabbe, ML, PMD, VWM, MFC, CAMFAK syndrome) · Central pontine myelinolysis · Marchiafava-Bignami disease · Alpers' Episodic/ paroxysmal Seizure/epilepsy Focal · Generalised · Status epilepticus · Myoclonic epilepsy Headache Migraine (Familial hemiplegic) · Cluster · Tension Cerebrovascular TIA (Amaurosis fugax, Transient global amnesia) Stroke (MCA, ACA, PCA, Foville's, Millard-Gubler, Lateral medullary, Weber's, Lacunar stroke) Sleep disorders Insomnia · Hypersomnia · Sleep apnea (Obstructive, Ondine's curse) · Narcolepsy · Cataplexy · Kleine-Levin · Circadian rhythm sleep disorder (Advanced sleep phase syndrome, Delayed sleep phase syndrome, Non-24-hour sleep-wake syndrome, Jet lag) CSF Intracranial hypertension (Hydrocephalus/NPH, Idiopathic intracranial hypertension) · Cerebral edema · Intracranial hypotension Other Brain herniation · Reye's · Hepatic encephalopathy · Toxic encephalopathy Spinal cord/ myelopathy Syringomyelia · Syringobulbia · Morvan's syndrome · Vascular myelopathy (Foix-Alajouanine syndrome) · Spinal cord compression Both/either Degenerative SA Friedreich's ataxia · Ataxia telangiectasia MND UMN only: PLS · PP · HSP LMN only: PMA · PBP (Fazio-Londe, Infantile progressive bulbar palsy) · SMA (SMN-linked, Kennedy disease, SMAX2, DSMA1) both: ALS central nervous system navs: anat/physio/dev, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc

v • d • e Non-Mendelian inheritance: anticipation Trinucleotide Polyglutamine (PolyQ), CAG Dentatorubral-pallidoluysian atrophy · Huntington's disease  · Kennedy disease · Spinocerebellar ataxia 1, 2, 3, 6, 7, 17 (Machado-Joseph disease) Non-Polyglutamine CGG (Fragile X syndrome) · GAA (Friedreich's ataxia) · CTG (Myotonic dystrophy type 1) · CTG (Spinocerebellar ataxia 8) · CAG (Spinocerebellar ataxia 12) Tetranucleotide CCTG (Myotonic dystrophy type 2) Pentanucleotide ATTCT (Spinocerebellar ataxia 10)