Background: Huntington's disease (HD) is a debilitating, hereditary neurological condition that results in the gradual degeneration and death of brain neurons. This neurodegenerative process primarily impacts the brain regions responsible for movement, cognition, and emotion. Ancient medicine in India, “Charak Samhita”, has also mentioned movement disorders, including Huntington’s disease (HD). Despite being regarded as an uncommon condition worldwide, Huntington's disease varies greatly in incidence depending on the region and population. Usually reported as 2–9 per 100,000, the frequency is higher among populations of European heritage (generally 5–10 per 100,000). The exact prevalence rate in India is not definitively known due to a lack of large-scale, population-level studies. Estimates by Indian researchers suggest a prevalence rate similar to European populations (approximately 3–7 per 100,000 people), which would translate to tens of thousands of affected individuals and over 200,000 people at risk in the country. However, its prevalence rate in India is not known. It is a progressive neurodegenerative illness that affects 2–9/100.000 of the general population. The usual onset is at around age 35–40 years, disease manifests clinically with many neurological and psychiatric symptoms. HD is caused by an expanded polyglutamine stretch in the N-terminal part of a 350 kDa protein called huntingtin (HTT). This stretch is encoded by a trinucleotide CAG repetition in exon 1 of HTT. An expansion of greater than 36 repeats results in HD. The number of repeats is inversely correlated with the age of onset of motor symptoms and the onset of disease. Neuropsychiatric symptoms may delay the appropriate diagnosis of HD and have major implications for disease management, prognosis and quality of life for patients and families. This study is about a 51-year-old male who came to the psychiatric outpatient department with late identification of Huntington’s disease after attending various clinics for the last 5 years, leading to a three-generation family tree of the disease in a small village near Ujjain, India. Methodology Patients were administered standardised measures of cognition, psychiatric symptoms, motor abnormalities, and a neuropsychological inventory (MMSE, UHDRS, DSR). Patient (N=10) in the family started on treatment with regular evaluation. Counselling is being done among successors to prevent the propagation of the disease and raise awareness against the “family curse” label for illness. Results The study has brought to light a spectrum of psychiatric symptoms leading to more disability in the course of HD, with all the patients exhibiting mild to moderate neuropsychiatric symptoms with/without chorea& dementia. Conclusions Available data suggest that there is a tendency for the affected descendant to present a larger CAG repeat expansion. Timely medical intervention and counselling have helped the affected family members and reduced propagation. The rural setting and limited financial resources have hindered medical management and research in this sample size.
The male patient, 52 years old, was brought to the psychiatric outpatient department service and hospitalized for insomnia, mood lability, dysphoria, forgetfulness, difficulty in daily activities and helplessness. There were no signs of hallucinations, delusions or formal thought disorder; the patient denied suicidal ideas. Psychotic or mood disorder diagnoses were excluded. The general physical examination revealed mild choreiform movements of the upper and lower limbs, as well as gait changes with slurred speech. The patient’s family declared that these disturbances started 8 years ago, but the patient neglected them. The patient did not use any psychoactive substance.
Huntington’s disease encompasses a catalogue of symptoms, including psychiatric, motor, and cognitive symptoms and chorea. HD is a germline adult-onset genetic disorder with abnormal CAG genetic expansions from birth, but typically does not develop sufficient signs and/or symptoms for clinical diagnosis till mid-adulthood. (1)
It is an autosomal dominant fatal genetic disorder leading to the progressive breakdown of nerve cells in the brain, with deterioration of a person’s physical and mental abilities during their prime working years. (2)
The hereditary neurodegenerative nature of Huntington’s disorder is caused by the abnormal expansion of a trinucleotide (CAG) repeat in the huntingtin gene on chromosome 4. Mostly, the time of onset is in the fourth or fifth decade of life, but the first symptoms can appear anywhere from childhood to old age, with the age of onset inversely correlated with the size of the triplet repeat expansion. The course of Huntington's disease is inexorable, usually leading to death within 15 to 20 years. (3)
Neural dysfunction is thought to precede neuronal death and brain atrophy; altered functional profiles during emotion recognition could provide a biomarker of disease evolution. Altered extrastriatal neural activation has previously been detected in subjects with pre-manifest Huntington's disease. (4)
Unfortunately, till date, Huntington’s disease has found no cure. The onset of symptoms may vary in each individual, with psychiatric manifestations as an integral part of the illness. (5)Predominating behavioural problems and psychiatric disorders are major constituents of the clinical spectrum of Huntington’s disease. (6) It is relevant as these neuropsychiatric symptoms have a substantially far more impact on the functional daily life of the individual compared to motor and cognitive dysfunctions. These conditions found in persons with HD strongly resemble an idiopathic psychiatric disorder. Depression has a high lifetime prevalence of about 30% to 40 %, with a suicide rate 4 to 6 times that of the general population. (7)
Depression may be accompanied by apathy, but it is not synonymous. Moreover, apathy is far more distressing to the caregiver and requires counselling. Mania, obsessive features, psychosis, perseverance, irritability, demoralisation and sexual problems form a part of the constellation. There may be the occurrence of non-specific symptoms like delirium along with dementia, which is subcortical in nature.
Manifestations of HD include the executive dysfunction syndrome of HD, appearing in individuals as apathy, irritability, disinhibition, impulsivity, obsession, and perseveration. Findings of a 134-person study showed symptoms which might be termed “apathetic,” such as loss of energy and initiative, poor perseverance and quality of work, impaired judgment, poor self-care, and emotional blunting, were the most common(12).
The rate of occurrence is highest in people of Western European descent, averaging around 7 per 100,000 people, while only about one case per million is recorded for people of Asian and African descent. Huntington’s disease has not only a neurological aspect but also a spectrum of psychiatric symptoms, which are not only linked to the stress and disability of the illness but are an integral part of the illness, repeatedly highlighted in various case reports.
Family History: Patient's father died of a similar illness by suicide at age 56 years. He had two marriages. Two of his real brothers also died of a similar disease with mania symptoms.
The routine admission blood work, including electrolytes, renal, hepatic and thyroid parameters as well as full blood count with differential, was all within normal limits. The neurological evaluation found low amplitude choreiform involuntary movements, dysarthria, mild bilateral ataxia, normal sensory and power examination, normal reflexes and mild cognitive impairment (18 points) on Mini-Mental State Examination. The Wechsler’s Deterioration Index results were normal (IQ = 98) and a deterioration index of less than 4 %. The EEG was normal, MRI shows atrophy of caudate nucleus and pallidus along with reduced volume.
Based on the clinical symptoms, a degenerative illness, such as Huntington’s disease, was suspected. Genetic testing for the HTT gene was performed. After the genetic test results had been obtained, the patient was reevaluated by the neurologist, who established the definite diagnosis of Huntington’s disease, confirmed both on clinical and genetic grounds. He is currently treated with small doses of Risperidone + Trihexyphenidyl (2+2 mg/day) and clonazepam (2 mg/day) with good results regarding behavioural and movement symptoms.
Figure 1: Family Pedigree.
After the detailed family history from the patient, a profile of similar patients was detected in the family, with some of his siblings dead. Among the rest, he encouraged his relatives and children, especially his daughter with similar complaints at age 24 years, to attend the psychiatric clinic. There are ten patients from the same family tree taking regular treatment at our hospital, with regular investigations and clinical evaluation done by a clinical psychologist using MMSE, UDRL, and DRS.
Patients were administered standardized measures of cognition, psychiatric symptoms, motor abnormalities and neuropsychiatric inventory. Patient (N=10) in the family started on treatment with regular evaluation. Counselling is being done among successors to prevent the propagation of the disease and raise awareness against the “family curse” label for illness.
RESULT
Active intervention helped 10 patients to seek treatment with a delay in the onset of neurodegenerative symptoms and relief in mood features. History and correlation could explain the cause of death of a few relatives and bring awareness to the successor. Counselling among successors to prevent the propagation of the disease. The study has brought to light a spectrum of psychiatric symptoms leading to more disability in the course of HD, with all the patients exhibiting mild to moderate neuropsychiatric symptoms with/without chorea& dementia.
DISCUSSION
The onset of the illness was correlated with the beginning of functional impairment, both professionally (he was early retired at the age of 51) and socially (he was widowed). The patient was not much aware of or impaired by the abnormal movements, and he did not seek medical consultation, as he considered it to be “a family curse”. However, the symptom that required medical attention, mostly at his requests, was the mood features (13-14). Often, people with HD may show reduced awareness of physical and mental changes in themselves.
CONCLUSIONS
Huntington’s disease is a rare condition which is frequently underdiagnosed, especially early on in the disease. This situation is caused by a lack of recognition of HD symptoms, which are often attributed to another disease by patients, family members and sometimes physicians. Available data suggest that there is a tendency for the affected descendant to present a larger CAG repeat expansion, which is believed to be responsible for a more malignant course of the disease. Timely intervention and counselling have helped this family with a delay in the onset of involuntary movements and reduced psychiatric problems with better functioning in daily life.
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