Hypercalcaemia mimicking Huntington’s disease: lessons learned from delayed diagnosis

Knowledge about some of the rarer causes of dementia is now quite advanced (Lautenschlager and Martins, 2005), which can in turn inform other more common causes of dementia. Such is the case with the monogenic disorder of Huntington's disease (HD) when compared to, say, Alzheimer's disease (AD). HD is an autosomal dominant hereditary neurodegenerative disease, which involves the basal ganglia, its connections to the frontal lobe and related neural circuits. The onset of HD is typically in mid-life (but onset can range from childhood to old age), with motor, cognitive and neuropsychiatric symptoms. There is currently no cure for this devastating and inevitably fatal neurodegenerative disease, with current treatment approaches being solely symptomatic. The highest frequencies of HD are found in Europe and in those countries whose populations are of predominately European origin such as the USA and Australia (approximately 1 case per 10,000 people).

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Molecular Mechanisms of Polyglutamine Pathology and Lessons Learned from Huntington’s Disease

Neurodegenerative Diseases - Molecular Mechanisms and Current Therapeutic Approaches ◽

10.5772/intechopen.93508 ◽

2021 ◽

Author(s):

Nagehan Ersoy Tunalı

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Molecular Mechanisms ◽

Lessons Learned ◽

Trinucleotide Repeats ◽

Cag Repeat ◽

Cag Repeats ◽

Disease Genes ◽

Polyq Diseases ◽

Dynamic Mutations

Identification of polymorphic repeating units on DNA as a cause of many neurological disorders has introduced a new concept in molecular biology: Dynamic mutations. Many of the identified dynamic mutations involve expansion of trinucleotide repeats within disease genes. Nine neurodegenerative disorders are currently known to be caused by expanding CAG trinucleotide repeats. These are Huntington’s Disease (HD), Dentato-Rubral Pallidoluysian Atrophy (DRPLA), Spinal and Bulbar Muscular Atrophy (SBMA), and Spinocerebellar Ataxia (SCA) Type 1, 2, 3, 6, 7 and 17. All are inherited in an autosomal dominant fashion except for SBMA, which is X-linked recessive. In all polyQ diseases, the disease mutation involves an increase in the number of CAG repeats within the coding regions of the respective genes. Since CAG triplets encode glutamine in the proteins, diseases caused by CAG repeat expansions are known as “Polyglutamine (polyQ) Diseases”. PolyQ diseases share certain clinical, neuropathological and molecular findings. The most widely studied polyQ disease is HD. In HD and other polyQ diseases, conformational change in the mutant protein causes abnormal folding and proteolysis of the protein, leading to the formation of a toxic polyQ fragment, which aggregates and causes neuronal dysfunction and selective neuronal death in the brain.

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Huntington's disease: Psychiatric practice in molecular genetic prediction and diagnosis

The British Journal of Psychiatry ◽

10.1192/bjp.170.2.146 ◽

1997 ◽

Vol 170 (2) ◽

pp. 146-149 ◽

Cited By ~ 9

Author(s):

Jane Scourfield ◽

Jo Soldan ◽

Jonathon Gray ◽

Gary Houlihan ◽

Peter S. Harper

Keyword(s):

Genetic Testing ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Social Services ◽

Molecular Genetic ◽

Lessons Learned ◽

Psychiatric Practice ◽

Genetic Prediction ◽

Testing Programme ◽

Direct Mutation

BackgroundPredictive genetic testing for Huntington's disease has been available in Cardiff since 1987 using linked genetic markers, and since 1993 using direct mutation testing, which can also be used as a diagnostic test. During this period there have been numerous referrals that have required liaison with psychiatric services at all stages of the testing programme.MethodA series of cases was selected to highlight issues from both genetic prediction and diagnosis that are relevant to psychiatric practice and have arisen during the testing programme.ResultsIssues have been raised concerning competence to consent to testing in the context of psychotic illness; depression and suicidal ideation in test candidates; requests for testing from third parties such as psychiatrists, social services and the courts; and testing of children.ConclusionsAs genetic testing becomes possible for more disorders the lessons learned from Huntington's disease will provide valuable guidelines for counselling.

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Lessons Learned from the Transgenic Huntington's Disease Rats

Neural Plasticity ◽

10.1155/2012/682712 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Rinske Vlamings ◽

Dagmar H. Zeef ◽

Marcus L. F. Janssen ◽

Mayke Oosterloo ◽

Frederic Schaper ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Nonhuman Primates ◽

Neuropsychiatric Symptoms ◽

Relevant Literature ◽

Lessons Learned ◽

Cag Repeats ◽

Transgenic Rat ◽

Cdna Fragment ◽

Transgenic Rat Model

Huntington's disease (HD) is a fatal inherited disorder leading to selective neurodegeneration and neuropsychiatric symptoms. Currently, there is no treatment to slow down or to stop the disease. There is also no therapy to effectively reduce the symptoms. In the investigation of novel therapies, different animal models of Huntington's disease, varying from insects to nonhuman primates, have been created and used. Few years ago, the first transgenic rat model of HD, carrying a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rathuntingtinpromoter, was introduced. We have been using this animal model in our research and review here our experience with the behavioural, neurophysiological, and histopathological phenotype of the transgenic Huntington's disease rats with relevant literature.

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Delayed diagnosis of spinal cord injuries in Huntington’s disease

Practical Neurology ◽

10.1136/practneurol-2020-002854 ◽

2021 ◽

pp. practneurol-2020-002854

Author(s):

Hamish D Morrison ◽

Dafydd Morgan ◽

Duncan J McLauchlan ◽

Catherine Clenaghan ◽

Anne E Rosser

Keyword(s):

Spinal Cord ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Spinal Cord Injuries ◽

Advanced Disease ◽

Neurodegenerative Disorder ◽

Psychiatric Symptoms ◽

Delayed Diagnosis ◽

Cord Injury ◽

Management Challenge

Huntington’s disease is a neurodegenerative disorder, characterised by progressive cognitive, motor and psychiatric symptoms. Patients with advanced disease presenting to emergency medical services can pose a diagnostic and management challenge for physicians unfamiliar with the condition. We describe two patients with Huntington’s disease in whom the diagnosis of traumatic spinal cord injury was delayed, discuss the role that cognitive bias and other factors played in this delay, and the lessons we can learn.

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