Abnormal red blood cells, known as acanthocytosis, have been identified in four unrelated Chinese adults with Huntington’s disease – undermining researchers’ attempts to differentiate the neurodegenerative disorder from another similar genetic disorder.
The researchers expected that the presence or absence of these abnormally shaped red blood cells would help distinguish between Huntington’s disease and a similar condition called neuroacanthocytosis, characterized by these misshapen, spiny red blood cells and neurological abnormalities. .
However, “in this study, we demonstrate four patients who present [Huntington’s] and acanthocytosis,” the scientists wrote, noting that these cases indicate that Huntington’s disease can coexist with abnormal red blood cells.
“Our study highlights the complexity and diversity of [Huntington’s disease]“, wrote the team.
The study, “Acanthocytes identified in Huntington’s diseasewas published in the journal Frontiers in Neuroscience.
Finding abnormal red blood cells in Huntington’s patients
Huntington’s disease is a genetic disease caused by excessive repetitions of a part of DNA, called CAG triplets, in the HT embarrassed. Healthy people normally have between 10 and 35 CAG repeats, but those with Huntington’s disease can have 36 to 120 repeats. Longer repetitions are linked to earlier disease onset.
Excessive CAG repeats lead to the production of a longer-than-normal huntingtin protein that accumulates to toxic levels inside brain nerve cells, causing progressive neurodegeneration.
With a wide range of signs and symptoms, the disease is primarily characterized by motor problems, with chorea – involuntary, jerky and irregular movements – occurring in the majority of patients. Other symptoms, including cognitive, behavioral and psychiatric problems, are often present before the onset of motor impairments.
A key issue for clinicians in making a diagnosis is that the hallmark symptom of chorea is also present in other diseases. An example is neuroacanthocytosis, an umbrella term for a group of rare genetic disorders whose hallmark is acanthocytosis and other abnormalities, especially movement disorders. Chorea is also the most common movement disorder associated with neuroacanthocytosis.
Abnormal or misshapen spiny red blood cells form clumps that cause degeneration of an area of the brain called the basal ganglia, which is responsible for controlling voluntary movement.
Huntington’s disease and neuroacanthocytosis “are two of the genetic causes of chorea,” the researchers wrote, adding that “it is sometimes difficult to tell them apart clinically because they have similar clinical symptoms and imaging findings.”
The presence of acanthocytes was believed to help distinguish the two disorders, as it is one of the main features of neuroacanthocytosis. But now, a team of researchers in China has described four cases of unrelated Huntington’s disease patients with acanthocytosis.
This combination “has not been previously reported,” the team wrote.
Finding data in red blood cells
Researchers analyzed red blood cell data from 40 adults with Huntington’s disease who were followed at Xuanwu Hospital, Beijing, from 2014 to 2022. They found that four (10%) – all Han Chinese , unrelated, ages 45-61, and disease duration 4-10 years – had acanthocytosis.
Chorea was found in all four patients, psychiatric symptoms in three and dementia in two.
The first patient, a 61-year-old man, had experienced rapid involuntary movements of the head and shoulders, progressing to the limbs, within the previous four years.
Her family reported irritability, delusions of persecution, and cognitive problems. In neuropsychiatric questionnaires, it showed a decrease in cognitive function. His sister and his father’s sister showed symptoms suggestive of Huntington’s disease from the age of 60.
The second patient, a 55-year-old man, had a 10-year history of chorea, which first affected his head and shoulders, then spread to limbs, face and tongue. Over the previous two years, he had developed personality changes and slurred speech. His mother and three siblings also showed involuntary movements.
A 45-year-old woman was the third patient and had a 10-year history of cognitive decline. At age 40, she developed involuntary repetitive movements of the mouth and face, slurred speech, and rapid involuntary movements in the limbs. The jerky movements occurred during waking hours and were absent during sleep.
Neurological examination showed speech disturbances, chorea, lack of limb and trunk coordination, decreased muscle tone and overactive reflexes. Further tests showed signs of moderate dementia. Family history showed movement disorder spanning three generations, affecting his mother, as well as his maternal uncle and grandmother.
The last patient, a 56-year-old woman, had presented with rapid jerky movements affecting the trunk and limbs for four years. According to her relatives, in the previous two years she had had a low mood, sleep problems, suicidal thoughts and slurred speech. These psychiatric symptoms appear before the motor symptoms.
On physical examination, she exhibited chorea-like movements of the trunk and limbs. She had no family history of movement or psychiatric disorders.
Blood tests for all patients were generally unremarkable, but brain MRIs showed signs of shrinkage of the caudate nucleus, a key part of the basal ganglia, and the outer layer of the brain.
The patients’ red blood cells were examined using a specialized microscope called a scanning electron microscope. The first patient had a low proportion, between 6 and 10%, of acanthocytes among his red blood cells; this proportion was high, greater than 20%, in the remaining patients. Normal ranges are less than 3% of the total red blood cell count.
Genetic analysis showed that all four patients carried a mutation in the HT gene, compatible with Huntington’s disease. The first patient carried 42 CAG repeats, the second 37 CAG repeats, the third 47 and the fourth 41. No other potentially pathogenic mutations were detected.
Based on the absence of both other typical symptoms and mutations in genes linked to neuroacanthocytosis, this condition “was ruled out,” the researchers wrote.
Taken together, these results show that Huntington’s disease can coexist with acanthocytosis, and that this can lead to an expansion of clinical symptoms, the team noted.
“Even though the primary genetic defect seems to be mostly directed to the brain, a peripheral defect can be seen in HD [Huntington’s disease]“, wrote the researchers.
“Meticulous clinical evaluation, laboratory tests and genetic study are essential to establish the final diagnosis,” they concluded.
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