This study will examine the origin and development of certain neurological diseases
involving abnormal metabolism. A significant number of patients with progressive
neurological disorders have not been diagnosed despite extensive workups. Lack of a specific
diagnosis may amplify the distress of both the patient and family and decrease the chance of
obtaining effective therapy. This study will try to advance the diagnosis and management of
Patients with a metabolic neurological disease of unknown cause or one which presents an
unusual or difficult management problem may be eligible for this study. This study does not
include patients with known or suspected leukodystrophy.
Participants will undergo various procedures, including physical and neurologic
examinations, blood and urine tests, and magnetic resonance imaging (MRI) to determine the
extent and severity of disease. MRI scanning uses a strong magnetic field and radio waves to
show structural and chemical changes in the brain. During the procedure, the patient lies on
a table in a narrow cylinder containing a magnetic field. He or she can speak with a staff
member via an intercom system at all times during the procedure. Patients will also have a
lumbar puncture (spinal tap) to examine the cerebrospinal fluid (CSF), which bathes the
brain and spinal cord. To obtain the fluid, a local anesthetic is administered and a needle
is inserted in the space between the bones in the lower back where the CSF circulates below
the spinal cord. A small amount of fluid is collected through the needle. Although spinal
fluid will not be examined regularly, this test may be requested during some clinic visits.
X-rays, nuclear medicine scans and consultations may be obtained as needed. Other tests may
include electroencephalograms (brain wave recordings), psychological tests, and speech and
language and rehabilitation evaluations. A skin biopsy may be done to grow cells in culture
for metabolic and genetic testing and to analyze the skin under a microscope. For the
biopsy, an area of skin is numbed with an anesthetic and a small circular area is removed,
using a sharp cookie cutter-type instrument.
First degree relatives (parents, children or siblings) of patients with a metabolic disorder
of unknown cause will be asked to provide a blood sample for DNA studies to try to identify
genetic basis of the disorder.
The study is expected to continue for 3 years, with yearly monitoring of patients for
changes in neurological, ophthalmological and general medical status.
On this protocol we will see patients of all ages with a neurodegenerative disorder of
unknown etiology, as well patients with known diseases that are atypical or present
difficult management problems. Patients with a known or a suspected leukodystrophy will be
excluded from this study. Lack of specific diagnosis amplifies the distress felt by patients
and families and decreases the chance of effective therapy. Clinical and laboratory
evaluation will include blood, urine, spinal fluid, peripheral tissue pathology and
- INCLUSION CRITERIA
Patients are those referred by their physician for a second opinion because of inability
to arrive at a diagnosis despite a reasonably complete evaluation.
Written informed consent given by the patient or his/her guardian.
Patients with a known or suspected leukodystrophy will be excluded from this study.
Patients who are unable to come to the NIH.
When no informed consent was given.
If on the opinion of the investigator, participation in this protocol will be to the
detriment of the patient.