Neuroacanthocytosis (NA syndromes) refers to 2 genetic disorders chorea-acanthocytosis and McLeod syndrome. The onset, severity and specific physical findings vary depending upon the specific type of NA present. Symptoms include chorea (involuntary, dance-like movements), unintentional movements of the face and tongue, progressive cognitive impairment, muscle weakness, seizures and behavioural or personality changes. The condition is ultra-rare: it is estimated that there are approximately 3,000 patients globally, although many of those are likely to be undiagnosed.
The diseases are associated with degeneration of the basal ganglia (the part of the brain that helps control movement) and loss of neurons in the brain and spinal cord. NA is typically an inherited autosomal recessive disorder and has been found to be caused by specific gene defects. The two core NA syndromes are chorea-acanthocytosis, increasingly also referred to as VPS13 Disease, and McLeod Syndrome, increasingly also known as XK disease.
For more information about both diseases you can view two presentations by Professor Adrian Danek for the European Reference Network. “VPS13A and XK bulk lipid transfer diseases” and “Neuroacanthocytosis syndromes, a rare chorea”
Researchers also benefit from access to the Leiden Open Variation Database which was set up to provide a flexible, freely available tool for genomic variant and phenotype collection, display and curation. LOVD allows both patient-centred and gene-centred views. LOVD is open source, released under the GPL license, and is actively being improved. On the server in Leiden, LOVD offers free hosting and support of LOVD-powered gene variant databases.
Symptoms may include grunts or tic noises made unconsciously in the throat, progressing to drooling and problems in controlling the tongue from ejecting food. Involuntary biting of the tongue, lips and/or cheeks may follow. There can be a general, slight physical awkwardness. Patients may knock items off shelves for no apparent reason. Difficulty with walking and balance can also be early symptoms. Problems controlling trunk, leg and arm movements are often barely observable at the beginning but become increasingly noticeable as the disease progresses. Many patients find it difficult to sleep at night, others report fatigue and weakness. Initial symptoms in chorea-acanthocytosis (VPS13 disease) are usually seen in the third decade of life, whereas in McLeod (XK disease) symptoms appear later and are of a slower progression.
NA syndromes are diagnosed through Western blot testing for the absence of specific proteins associated with each sub-type of NA. For example, the Western blot test allows doctors to detect the presence of the protein “chorein”. If it does not not appear, VPS13 disease, is likely. For VPS13 disease as well as McLeod syndrome, the definitive diagnosis is made with DNA testing.
There are no curative therapies for NA disorders. Treatment is symptomatic and supportive. Antipsychotic drugs that block dopamine, such as haloperidol, can provide temporary relief from tics and chorea. Drugs used to decrease anxiety, such as diazepam, can also decrease movement disorders which are often made worse by associated stress. Other drug therapies may include anticonvulsants and antidepressants.
Proper nutrition and hydration are important as well as maintenance of all skills for as long as possible. A feeding tube may be needed for some patients as the disorder progresses.
Speech, occupational and physical therapies may provide some relief and encourage confidence. Deep brain stimulation has periodically helped some patients (although not everyone responds to it) and injections of Botulinum Toxin can relax muscles and reduce unintentional movement.