Red blood cells are disc shaped cells that carry oxygen in the blood. There are various disorders that can lead to an abnormal shape of these cells. The term acanthocytosis describes the presence of distorted red blood cells (acanthocytes) in the blood. The cells become denser and irregularly shaped with spiculated (sharp spur-like) protrusions. The normal shape of red blood cells are determined by certain proteins in its cell membrane. When there are certain defects or deficiencies of these proteins, abnormal shapes of the red blood cells are seen. However, these proteins are also common to other types of cells in the body like the nerve cells and brain tissue. This collectively leads to certain conditions marked by abnormalities of both the red blood cells and disturbances in brain function.
Neuroacanthocytosis (NA) describes a range of neurological conditions that arise with inherited abnormalities in red blood cells. The disturbances of the nerves that are present with neuroacanthocytosis affects movement and personality traits. Neuroacanthocytosis is diagnosed by the presence of characteristic star-shaped red blood cells at any stage of disease. Initial onset of the disease may occur either during infancy or adulthood. The neurological symptoms may not be evident at the outset. Overall the condition is found to be more prevalent among males.
Neuroacanthocytosis does not refer to a single condition. Instead it is a group of rare diseases that couple neurological symptoms with blood cell abnormalities. Although neuroacanthocytosis is caused due to defect in genes associated with metabolism, it manifests itself as abnormal brain and nerve functioning. Often these genetic defects cause damage of brain areas that regulate body movements (caudate and putamen). Death of neurons or inflammatory responses from glial cells may lead to neurotic disorders.
Medical literature suggests that impaired metabolism of lipoproteins presents symptoms common to neuroacanthocytosis. Owing to the fact that brain cells are rich in lipoproteins and that red blood cells membranes are also rich in lipoproteins, neuroacanthocytosis diseases are classified into two categories.
Neuroacanthocytosis with impaired lipoprotein metabolism
- Also known as Bassen-Kornzweig disease or abetalipoproteinemia having elevated serum lipoprotein levels.
- It is an autosomal recessive disease.
- Typically presents in infants and children.
- Common symptoms include ataxic or dancing gait along with acanthocytosis.
- Hypobetalipoprotenemia also belongs to the same class of neuroacanthocytosis.
- Also known as Levine-Critchley syndrome or Choreiform neuroacanthocytosis.
- Presents with no change in serum lipoprotein levels.
- Typically considered late onset, choreiform neuroacanthocytosis is often seen in mid-age around 30 to 35 years and may progress further.
- It is an autosomal dominant disease showing symptoms common to Huntington disease including involuntary rapid, jerky movements (chorea) and forgetfulness along with acanthocytosis.
- Other diseases grouped under this category :
– Huntington disease-like 2 (HDL2)
– Chorea acanthocytosis (ChAc)
– McLeod syndrome (MLS)
– Pantothenate kinase-associated neurodegeneration (PKAN)
Elevated level of creatine phosphokinase (CPK) and rarely, serum transaminases, are considered to be major reasons for distortions in red blood cells.
Neuroacanthocytosis is caused due to genetic abnormalities. The symptoms of most of the neuroacanthocytosis diseases are common. However, only upon genetic analysis is the actual cause of the disease known. Defects in the genes responsible for lipoprotein metabolism leads to hereditary lipoprotein disorders-related neuroacanthocytosis.
Inherited movement disorders that show symptoms common to Huntington’s disease are usually multigenetic traits or occur spontaneously. Although a number of genes responsible for presentation of neuroacanthocytosis-related symptoms are known, the exact pathophysiological mechanism is poorly understood.
Lipoprotein metabolism-associated NA has defects in genes coding for betalipoproteins or proteins that help in uptake of these lipoproteins. Overall these genetic defects impair absorption of vitamins, importantly vitamin E and other nutrients. Vitamin deficiencies often have serious impacts on overall brain functioning and also leads to defects in membrane composition of RBC.
The pathophysiology and the etiology of other genetic NA diseases are not well understood. However, in some way or the other these defects alter the RBC membrane properties.
Individuals suffering from some severe, active form of other related diseases are more likely to develop neuroacanthocytosis.
Common symptoms of neuroacanthocytosis include:
- Involuntary rapid movements of limbs, tongue and mouth
- Parkinsonism – motor disorders characterized by incessant tremors and jerks.
- Changes in personality traits – antisocial, depressed, impulsive, anxious and unaffected or insensitive to other’s emotions.
- Severe feeding difficulties – due to difficult jaws and mouth movement; develop profound weakness.
- Abnormal speech
- Involuntary tongue and lip biting
- Gait problems – due to excessive, involuntary twisting of feet and knees.
- Unable to hold neck and head properly, often leaning to sides.
- Seizures, in some cases
- Involuntary, exaggerated responses towards sudden appearance of any object or context – impaired decision-making ability; unable to decide before executing any response.
- Impaired memory recall ability
Neuroacanthocytosis is diagnosed through blood test that shows:
- Presence of 10% to 30% of deformed RBCs or acanthocytes
- Elevated creatine kinase level
- Increased amount of betalipoproteins in the serum (in case of lipoprotein-metabolism related NA)
- Elevated liver enzymes
- Screening defective genes
- CT scans, MRI or PET imaging techniques could be helpful in studying changes in the brain that may present neurological symptoms.
- Functional tests including electromyography and nerve conduction tests are helpful in assessing the proper coordinated functioning of muscles and nerves.
While the lipoprotein-metabolism related disorders can be managed effectively, there is no cure for the choreiform-neuroacanthocytosis group. Intake of high doses of vitamins, especially vitamin E, A and K ameliorates neuroacanthocytosis symptoms in lipoprotein-related group. Treating the symptoms offers the best therapeutic strategy for multigenetic Huntington disease related neuroacanthocytosis.
Medication with least side-effects are usually considered the best options. Symptoms that are more likely to be treated with certain drugs includes :
- Involuntary movements – haloperidol
- Tremors and jerks – carbidopa or levodopa
- Spasm of face and jaw muscles – botulinum toxins
- Psychotic illness and other neurological symptoms
- Memory loss
Other treatment options
Psychiatric guidance proves valuable in managing depression and serious changes in behavior and personality traits. Body weakness is the major cause of death in NA patients. Poor feeding habits caused due to impaired jaw movements, affect general body health. Maintaining a good diet and proper feeding habits may prove helpful in restoring overall health. In extreme cases, semi-solid food and implantation of feeding tube may offer relief. Additional supports like wheel chairs or walking stands may be used for normal assistance.