Neuropsychological assessment in X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a rare genetic metabolic disorder. The
clinical spectrum is broad with involvement of the adrenal glands, myelum and
peripheral nerves. Some, but not all, develop a devastating and fatal
progressive cerebral demyelinating disease, which can be treated with
haematopoetic stem cell transplantation (HSCT). Candidates for transplantation
are selected depending on the severity of MRI abnormalities and
neuropsychological testing results. The latter are used to evaluate functional
consequences of demyelination. Low Performance Intelligence Quotient scores (<
80) are associated with decreased functional outcome after HSCT. Neurocognitive
function in patients not (yet) affected by cerebral demyelination is thought to
be normal, although previous published results are inconsistent.

In 52 patients with a mean age of 6.4 years (range 2.1-14.6) with normal brain
MRI, neuropsychological testing did not reveal any cognitive deficiencies when
tested as a group, although 4 individual participants had moderate deficiencies
in some cognitive functional domains. The authors assumed these deficiencies
were probably not related to X-ALD.
In another group of boys without radiological abnormalities (age range
3.92-14.58 years) 2/8 patients had a significantly lower Performance
Intelligence Quotient in comparison to the Verbal Intelligence Quotient, in 3/6
patients Kaufmann Asessment Battery for Children was significantly decreased
and in 5/7 Frostig Developmental Test of Visual Perception results were
abnormal.
In a group of 12 adult patients neurocognitive evaluation was solely abnormal
in the 3 patients with cerebral disease7. Controversially, neuropsychological
testing in 57 adult patients (41 males and 16 females) revealed cognitive
dysfunction in 60%. The pattern of impairment was mostly subcortical with
defects in frontal-executive functions and memory. It is unclear however how
many of these patients were affected by active cerebral demyelinating disease
when tested.

We aim to assess neuropsychological function in X-ALD patients without active
cerebral demyelinating disease and to correlate these findings to neuroimaging
data. Now that newborn screening may be implemented in The Netherlands this
data will be particularly valuable to expand our knowledge of the disease
spectrum.

The primary objective is to assess neuropsychological function in X-ALD
patients without active cerebral demyelinating disease. Data of minors will be
compared to matched healthy controls. Data of adults will be compared to
reference values. The second objective is to correlate these findings to MRI
imaging data.

This study is a cross-sectional cohort study, requiring one visit to the
hospital.

Research on rare diseases is often restricted by the maximum cohort size
available for studies. To investigate the neurocognitive function of X-ALD
patients it is especially important to include minors because they form a
significant section of the cohort. Taking in mind that newborn screening for
X-ALD will be implemented in the Netherlands the necessity to expand our
knowledge on all aspects of the disease spectrum in the different age groups
is higher than ever. The number of newly diagnosed patients will rise
substantially and thorough studies have to be done to be able to inform parents
as completely as possible. Moreover, the results of this study have the
potential to improve individual patient care if results suggest neurocognitive
problems in X-ALD patients. This test battery is relatively brief and therefore
not suitable to make any individual statements. However when indicated
appropriate follow-up will be initiated. Risks of participation are negligible
and the burden of a NPA is considered minimal. The tests are conducted
playfully and are usually not considered tedious by children.