The purpose of this study is to learn about heart and skeletal muscle problems related to
neuroacanthocytosis (also called Mcleod's syndrome and Levine-Critchley disease). This
inherited condition causes problems of blood, brain, heart and muscle function. About 60
percent of patients have an unusual heart muscle abnormality that increases the risk of
sudden death. Although the molecular (genetic) changes responsible for neuroacanthocytosis
have recently been identified, the heart and skeletal muscle problems are not well
understood. This study will try to correlate the specific genetic abnormalities with the
clinical features of the disease and identify possible causes of sudden death.
Patients and first degree relatives of patients with neuroacanthocytosis 18 years of age or
older may be eligible for this study. Participants will be admitted to the National
Institutes of Health Clinical Center for 2 to 5 days for the following tests:
- Electrocardiogram - to measure the electrical function of the heart
- Echocardiogram - uses ultrasound to measure heart thickness and detect heart vessel
- Cardiac magnetic resonance imaging (MRI) - uses a magnetic field and radio waves to
provide pictures of the heart for measurements of muscle thickness and muscle function
- Exercise testing on a stationary bicycle - to measure and record symptoms during
exercise, exercise duration, heart rate and blood pressure, oxygen consumption and
- Holter monitoring - uses a device attached to the chest for continuous recording of
- Blood tests - to look for muscle damage, to exclude other causes of muscle disease, and
to perform DNA (genetic) testing
- Neurological consultation - to test muscle function, coordination and tests of certain
brain functions such as memory and concentration
Patients with evidence of muscle disease may also undergo a muscle biopsy. This is done
under a local anesthetic and possibly small amounts of sedation. A small area of skin over
a large arm muscle (biceps) is numbed, a short incision is made and a small sample of muscle
tissue is removed for microscopic examination.
Patients with evidence of heart disease may also undergo the following additional tests:
- Cardiac catheterization and electrophysiological study - to determine the extent of
heart disease and study abnormal heart rhythms. Cardiac catheterization is done under
mild sedation. The groin is numbed with an anesthetic and catheters (thin plastic
tubes) are inserted and passed through the blood vessels into the chambers of the
heart. Pressures inside the heart are measured and pictures may be taken of the heart
arteries. During this procedure an electrophysiology test may be done to study
abnormal heart rhythms.
- Cardiac biopsy - to examine heart muscle tissue. This may be done at the end of the
cardiac catheterization. Small samples of heart muscle are obtained using a fine
instrument passed through the catheter in the groin.
Family members who do not have signs of heart or muscle disease will only undergo
non-invasive tests. All participants will be given the results of all tests and treatment
options will be discussed.
Neuroacanthocyoses (NA) are rare, closely related clinical syndromes characterized by
neurological features and erythrocyte acanthocytosis. Most have a skeletal myopathy as
indicated by persistently elevated plasma creatinine kinase, and about 60 percent of the
patients have an unusual cardiomyopathy with increased risk of sudden death. The molecular
causes of the syndromes have very recently been defined. However, cardiac and skeletal
muscle involvement and outcomes have been poorly described and causes of sudden death are
unknown. We propose to (1) describe the cardiac and skeletal muscle findings of NA and to
identify potential mechanisms of sudden death; (2) correlate the molecular causes of NA with
its cardiac and skeletal expressions; and (3) define the specific phenotype, if any,
associated with the heterozygous state.
Patients of either gender, aged greater than or equal to 18 years, with previously
diagnosed NA or with clinical features consistent with that diagnosis.
First degree family members of either gender, aged greater than or equal to 18 years, of
patients with NA and relatives proven to be heterozygous for the disease genotype.
Positive pregnancy test.