Comparison of Core Neuroacanthocytosis Syndromes

Comparison of Core Neuroacanthocytosis Syndromes

Stephanie A. Sminkey

Abstract

This paper will concentrate on a brief educational exploration of the four core neuroacanthocytosis syndromes (NA) and what a neuroacanthocytosis syndrome is defined. In addition it will provide more in depth information into the four core syndromes listed as follows: McLeod Syndrome (MLS), Chorea acanthocytosis (ChAc), Huntington's disease - Like 2 (HDL2), and Pantothenate Kinase associated neurodegeneration (PKAN). The following data will be provided on each of the core syndromes: clinical characterization, diagnostic procedures and considerations, management, and prognosis. In turn, the reader's knowledge base will be increased regarding all four of the defined rare and obscure syndromes listed above.

Comparison of Core Neuroacanthocytosis Syndromes

Neuroacanthocytosis syndrome refers to in the medical field. Neuroacanthocytosis syndromes refer to a group of syndromes which are heterogeneous8 with nervous system abnormalities. They are composed of substances and or natures that are unalike\8. They are also conjoined with deformed erythrocytes. In a normal healthy person, erythrocytes or mature red blood cells10 have a biconcave lens shape5. Biconcave is defined as concave on both sides unlike the erythrocytes found in a normal healthy adult the erythrocytes in an individual with a neuroacanthocytosis syndrome are deformed. 10 These erythrocytes are misshapen and have spike like protrusions within the erythrocytes and often have a thorny appearance.7,9

According to Jung, Hans H, Danek Adrian, Walker, Ruth H's review article Neuroacanthocytosis (2009); "Neuroacanthocytosis syndromes are genetically defined neurodegenerative disorders with a Huntington-like phenotype".7 Neuroacanthocytosis syndromes are genetically characterized as deteriorations of the nervous system with a resemblance to Huntington's when compared symptomatically or upon laboratory testing.10 The normal age of onset is 25-45 and is marked by abnormalities in the neurological system.10

Neuroacanthocytosis is divided into two large groups of syndromes, the core and those conjoined with lipoprotein disorders10. We will begin to explore and try to place some understanding to the first group of these, the core neuroacanthocytosis syndromes. There are four core neuroacanthocytosis syndromes. Chorea-acanthocytosis, McLeod syndrome, Huntington's disease - like 2, and Pantothenate kinase are all associated with neurodegeneration.7 The core neuroacanthocytosis syndromes are defined as autosomal recessive4 or as appearing on a chromosome other than the sex chromosomes X and Y and being a recessive trait as opposed to dominant.10 McLeod's Syndrome being the only deviation, and having an X linked recessive origin.

Clinical characteristics or signs and symptoms of Chorea acanthocytosis may include the following: normal age of onset 20, feeding dystonia10 (prolonged involuntary muscular contraction that may cause twisting of body parts) conjoined with tongue protrusion10 (projecting out of the mouth) after contact with food, orofacial (referring to oral and facial) dyskinesias (defect in the ability to perform voluntary movement or uncontrolled involuntary movements)10, neuropathy10 (disease of the nerves) in extremities, variable weakness caused by genetic mutation4, limb chorea (involuntary dancing or writhing of the limbs or facial muscles10, parkinsonism10 (showing similarities or being misdiagnosed as Parkinson's), dysphasia10 (inability to swallow), dysarthria10 (clumsiness of speech or difficulty forming words), patients may bite tongue, the inside of their cheeks, and their lips accidentally, seizures in approximately 50% of patients particularly upon onset3, myopathy10 (focal or diffused muscular weakness), atrophy (decrease in the size of a muscle or tissue), Life expectancy is reduced, and the average ages of death are 28-61 years of age.3

Because Chorea acanthocytosis is a neurodegenerative disorder, its effects are every bit as wide as the nervous system itself. There are only 500-1000 documented cases worldwide. Diagnostic procedures and considerations for Chorea acanthocytosis may be inclusive of: muscle biopsy, electromyography10 (graphic record of voluntary and involuntary muscle contractions), Magnetic Resonance Technology (MRI), demonstration of adverse changes in the nervous system, computed tomography (CT) revealing atrophy of the caudate nuclei with dilation of the anterior horns of the lateral ventricles, blood serum revealing increased serum levels, molecular genetic testing of VPS13A, blood samples for acanthocytes and Chorein Western Blot testing on a research basis4.

Management for Chorea acanthocytosis could include the following interventions: EEG every 3 years, nutritional management and monitoring, Botox for oro-facio-bucco-lingual dystonia, medication interventions for seizures management, feeding assistance, speech therapy, protective devices, splints, medications for emotional management, dopamine antagonist, deep brain stimulation might also be considered, however outcomes are variable and data is limited. 3

McLeod Syndrome was named after Hugh McLeod, a Harvard dental student who was noted first to carry the XK gene. The XK gene is the only one known to be specifically linked to McLeod's Syndrome.9 McLeod syndrome only presents around 150 cases worldwide.8 Clinical Characteristics may present similar to other neuroacanthocytosis syndromes and may include: onset of the disease process occurs between 28-61, abnormal star-shaped erythrocytes, myopathy, atrophy, limb chorea, peripheral neuropathy2 (reduced sensation and weakness of the arms and legs), dystonia, vocal tics, behavioral changes (self-care deficits, obsessive compulsive disorder, psychosis, depression, or anxiety) may be among earliest symptoms, 60% of patients have a co-morbidity of cardiomyopathy10(muscle weakness pertaining to the heart) conjoined with atrial fibrillation10(most common cardiac dysrhythmia marked by rapid irregular electrical activity in the atria or top of the heart) and /or malignant arrhythmias, dilated cardiomyopathy7, Approximately 50% display a comorbidity of generalized seizure disorders, cognitive deficits, cardiac complications exist even in asymptomatic carriers of the McLeod Blood Group.8,2

Diagnostic procedures for McLeod Syndrome include: magnetic resonance technology (MRI), demonstration of adverse changes in the nervous system, computed tomography (CT), liver enzyme panels revealing increased serum levels, blood test revealing acanthocytes, molecular genetic testing for the absence or shortened nature of