Huntington’s Disease

Huntington’s Disease

Definition: incurable, progressive, autosomal dominant neurodegenerative disorder characterised by progressive chorea and dementia, typically commencing in middle age.

Aetiology/ risk factors:

-Genetic, autosomal dominant = extensive expansion of CAG repeat on chromosome 4, huntingtin gene which codes for the protein huntingtin = toxic gain of function of protein

-Leads to atrophy and neuronal loss of striatum (of basal ganglia) and cortex

-Exhibits anticipation = earlier age of onset in each successive generation

Epidemiology:

-Worldwide prevalence is 8 in 100,000.

-Rare in East Asian populations.

-Presents in middle age. Average age of onset 30-50 years.

Symptoms & Signs:

Often there is a prodromal phase of mild symptoms:

Early cognitive, emotional and behavioural changes-

-irritability, emotional lability

-dysphoria (general dissatisfaction), depression

-metal inflexibility, anxiety

incoordination– progressive fidgeting and clumsiness

Image result for chorea
Later:

chorea = a flow of involuntary jerky movements, flitting from one limb/muscle to another (each seemingly a fragment of a normal movement)

-often accompanied by grunting and dysarthria (motor speech problem)

 

dementia

+/- fits

-Patient may become rigid, akinetic and bed-bound in late disease

Other signs:

-slow voluntary saccades and supranuclear gaze restriction

-parkinsonism and dystonia (muscle spasms)-  especially in juvenile-onset disease

-mental state examination reveals cognitive and emotional deficits

Investigations:

Genetic analysis: diagnostic if > 39 CAG repeats in HD gene.

Intermediate repeat lengths (27-39) exist with reduced penetrance.

Brain MRI/CT- may show symmetrical atrophy of striatum, particularly the caudate nuclei, and butterfly dilation of the lateral ventricles

Image result for huntington's disease ct mri

Image result for huntington's disease ct mri

Image result for acanthocytosis
Bloods-may be needed to exclude other pathology

e.g. caeruloplasmin (Wilson’s), TFTs, ESR,

blood film (acanthocytes = spiky RBCs- seen in chorea acanthocytosis)

Management: no treatment prevents progression

-For chorea = dopamine antagonists e.g. TETRABENAZINE

Antidepressants for depression

-Atypical anti-psychotics for psychosis

-MDT approach including: occupational therapist, speech and language therapist, dietician

-Psychological support for patient and family

-Genetic counselling of patient and family

Complications:

-50% of offspring will carry the Huntington’s disease gene

-High risk of depression, attempted suicide (28%) and suicide (7%)

Prognosis:

-Death within approx. 15 years of diagnosis, usually from a respiratory tract infection.

References: Cheese & Onion, Rapid Medicine
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