Neuroacanthocytosis

What is Neuroacanthocytosis?

Neuroacanthocytosis is a term for a few hereditary disorders, which leads to unusually shaped red blood cells (acanthocytes) and gradual worsening of brain-related functions. People affected by these conditions can show a broad range of symptoms, that can vary quite a bit. Common features include issues with movement (movement disorders), damage to nerves (neuropathy), mental health issues, decline in thinking ability (neurocognitive degeneration), and seizures.

There are many diseases in this category but the key ones include chorea-acanthocytosis (ChAc – an inherited movement disorder), McLeod syndrome (MLS – a genetic multi-system disorder), Huntington like-disease 2 (HDL2 – a neurodegenerative disorder), pantothenate kinase-associated neurodegeneration (PKAN – also called Hallervorden Spatz disease), HARP Syndrome (part of the PKAN family, featuring various symptoms such as night blindness, misshapen red blood cells, and nerve damage), abetalipoproteinemia (ABL – a condition which impairs the normal absorption of dietary fats), hereditary hypobetalipoproteinemia (HHBL – a disorder related to the body’s ability to fully absorb dietary fats), and aceruloplasminemia (a disorder that affects iron metabolism).

The two core conditions in this group are chorea-acanthocytosis and McLeod Syndrome. Each disease in the neuroacanthocytosis family is extremely rare – for example, PKAN affects fewer than 1 to 3 out of every 1,000,000 people, and ABL is so rare that fewer than 100 cases have ever been reported.

What Causes Neuroacanthocytosis?

Neuroacanthocytosis syndromes are caused by a variety of different genetic changes that are passed down in families in different ways. The most common way these genes are passed down is through what’s called autosomal recessive inheritance (which means that both parents must carry and pass on the faulty gene).

Other syndromes, like McLeod syndrome, are passed down in an X-linked recessive way. This means that the condition is linked to the X chromosome and typically affects males more frequently, as they only have one X chromosome. On the other hand, Huntington-like disease 2 and hereditary hypobetalipoproteinemia are passed down through what’s called autosomal dominant and codominant patterns. This means either a single copy of the faulty gene from one parent can cause these conditions or both copies of a gene from each parent must have changes.

Huntington-like disease 2 (HDL2) happens because of the expansion of a specific section of a gene (JPH3). This is similar to what happens in Huntington’s disease. Patients with HDL2 may experience worsening symptoms with each generation depending on the extent of the gene expansion.

It’s important to note that all these diseases can appear differently and be more or less severe, even within the same family. This is because they vary in genetic penetrance (the likelihood that a gene will cause a trait to appear) and phenotypic manifestations (the actual symptoms a patient experiences).

Risk Factors and Frequency for Neuroacanthocytosis

Neuroacanthocytosis syndromes are very rare, with some populations showing a higher prevalence than others. For instance, HDL2 is more frequently reported in people of African descent, while PKAN is more common in certain areas of the Netherlands and the Dominican Republic.

Signs and Symptoms of Neuroacanthocytosis

Neuroacanthocytosis syndromes refer to a group of conditions characterized by specific neurological, neuromuscular, or neuropsychiatric symptoms. Affected individuals usually show progressive movement abnormalities (like unsteady movement or too much movement), declines in cognitive functions, and changes in behavior. These symptoms vary depending on the specific type of neuroacanthocytosis syndrome a person has.

If a clinician suspects that an individual could have a neuroacanthocytosis syndrome, a thorough physical examination is necessary. This involves looking at various aspects such as:

• Physical health
• Neurological health (brain and nerves)
• Reflexes
• Cranial nerves (relating to the brain and face)
• Gait (the way the person walks)
• Muscle strength
• Mental status (cognitive and emotional wellbeing)

Understanding the patient’s medical history is also crucial in diagnosis. If a person shows a clear history of progressive neurological, neuromuscular, or neuropsychiatric symptoms that don’t align with other common diseases, it may indicate a neuroacanthocytosis syndrome. Any prior medical records, family history, additional information from family members, and previous genetic testing results can be helpful in making a correct diagnosis and determining the most suitable tests for further evaluation.

Testing for Neuroacanthocytosis

In some health syndromes, the signs and symptoms can guide doctors to use additional tests to confirm the diagnosis. These tests often include magnetic resonance imaging (MRI) or computed tomography (CT) scans to check for any neurological issues in the brain or spinal cord tissues. Besides, blood tests can also help rule out some diseases or confirm others. This is especially true for diseases related to lipoproteins (like ABL and HHBL) or for a condition called aceruloplasminemia.

For several disorders known as neuroacanthocytosis syndromes, there are either no clear diagnostic criteria like in ChAc, ABL, and HHBL, or genetic testing is required. Genetic testing can help to identify certain diseases that may otherwise seem similar to other conditions, like in the case of HDL2.

Treatment Options for Neuroacanthocytosis

Unfortunately, there are currently no cures or definitive treatments for several conditions grouped together as neuroacanthocytosis syndromes, including ChAc and MLS. These are conditions that affect both the nervous system and red blood cells. The exceptions are conditions known as ABL, HHBL, and aceruloplasminemia, for which there are specific treatments.

For the remaining conditions, the focus is generally on three main goals:

1) First, we aim to relieve or reduce symptoms as much as possible.

2) Second, we strive to slow down the symptoms that could get worse over time.

3) Lastly, we emphasize preventing severe problems that can greatly affect health and quality of life. These can include issues with the eyes, imbalances in metabolic or hormonal function, seizures, heart problems, and serious muscle contraction disorders known as status dystonicus.

Given the complexity of these conditions, they affect various parts of the body, from nerves to blood cells to multiple organ systems. Therefore, it’s recommended that a team of various kinds of healthcare professionals look after patients. This team might include specialists in the brain and nervous system, mental health, eyes, and genetic disorders. They work together to identify, evaluate, and manage the care of patients diagnosed with neuroacanthocytosis syndromes.

What else can Neuroacanthocytosis be?

When diagnosing unusual health conditions, the symptoms can often be similar to numerous other illnesses. So, it might be difficult to differentiate them without the right medical tests. These tests could involve imaging procedures, laboratory tests, or even genetic analyses.

What to expect with Neuroacanthocytosis

The outcomes for different medical conditions can greatly vary. Conditions like ChAc, MLS, typical PKAN, and HDL2 are usually chronic – meaning they last for a long time – and progressive, which means they get worse over time. They often lead to problems with speech, resulting in issues like poor nutrition and lung infections from accidental inhalation of foreign materials, which could eventually lead to death. In some instances, additional symptoms such as seizures, heart rhythm disorders, heart muscle disease, and frequent muscle contractions can cause early death.

However, the severity and progression of conditions like aceruloplasminemia, ABL, and HHBL are heavily reliant on proper management. This would involve the usage of specific medicines known as chelating agents and supplements of fat-soluble vitamins. If managed correctly, patients with these conditions can expect to live a regular lifespan.

Possible Complications When Diagnosed with Neuroacanthocytosis

: The complications from neuroacanthocytosis syndromes are usually due to problems with the nerves and muscles or a decrease in cognitive abilities. Symptoms can include muscle spasms, problems with coordination, muscle disease, uncontrollable movements, loss of certain nerve paths, or spinal cord issues. This can lead to challenges in walking and difficulties in carrying out everyday activities. The situation can be more complicated by additional cognitive issues such as personality changes, impulsivity, aggression, or mental health symptoms.

Patients diagnosed with a neuroacanthocytosis syndrome can also face life-threatening complications such as seizures, irregular heart rhythms, heart disease, severe movement disorders, and mental health problems possibly leading to self-harm.

Eye-related complications such as retinal degeneration and retinopathy (damage to the retina of the eyes) are common in similar conditions like PKAN, ABL, HHBL, and Aceruloplasminemia.

In some conditions that are driven by metabolic issues like ABL, HHBL, and Aceruloplasminemia, multiple bodily systems can be involved, which may lead to anemia, diabetes, enlargement of the heart and liver, and low thyroid hormone levels.

Potential Complications:

• Muscle spasms
• Coordination issues
• Muscle disease
• Uncontrollable movements
• Spinal cord issues and nerve damage
• Difficulties in everyday activities
• Personality changes
• Impulsivity and aggression
• Mental health problems
• Seizures
• Irregular heart rhythms
• Heart disease
• Movement disorders
• Eye-related complications
• Anemia
• Diabetes
• Heart enlargement
• Enlargement of the liver
• Low thyroid hormone levels

Preventing Neuroacanthocytosis

Talking with a genetic counselor can be an important part of treatment. The genetic counselor can give helpful information and support not just to the patient, but to their family as well. Visits with this specialist can explain important medical facts such as what the genetic disease looks like (phenotypic characteristics), which genes are causing the illness (genotypic characteristics), how the disease might progress, and the chances that other family members or children might also get the disease.