MLD is a rare disorder where the diagnosis is often missed or delayed because it is not the first cause that comes to mind when a patient presents with symptoms. In young children, MLD is often confused with cerebral palsy or other
causes of developmental delay. In older children, it is frequently confused with Batten disease, attention-deficit
hyperactivity disorder (ADHD), or adolescent/puberty-related mood/behavioral changes. In adults, psychological conditions
are often suspected. In order for a healthcare professional to correctly diagnose MLD, a variety of tests must be performed.
A magnetic resonance image (MRI) of the brain may be the first indicative test a patient undergoes. An MRI shows the different tissues in the brain and highlights the presence or absence of myelin sheaths around the nerve cells as well as patterns of demyelination. Patients must remain completely still for up to 30 minutes while having an MRI; therefore, many patients,
including most children, require sedation during the procedure. The images below show a cross-section of a normal brain and
the brain of a patient with MLD.
Normal axial brain MRI (left) and MLD axial brain MRI (right)
Urine and blood samples are required for a formal diagnosis of MLD (an MRI is not definitive in diagnosing the disease
because an abnormal MRI could be a result of other conditions). The blood ASA enzyme levels are measured first, followed
by urine sulfatide levels and clinical analysis. An increased amount of sulfatide in the urine indicates that the ASA enzyme
is not breaking down sulfatides, which usually suggests MLD. A low level of ASA enzyme in the blood is not a definitive test
for MLD because these same low levels of ASA are also found in a condition called ASA pseudodeficiency. (ASA pseudodeficiency
is a condition that results in individuals having only 5% to 15% of ASA enzyme function. However, this deficiency does not
appear to pose a health risk and individuals do not develop MLD. ASA pseudodeficiency is present in about 1% to 2% of
Europeans.) So the diagnosis of MLD must be confirmed with other tests, including urinary sulfatide measurement.
An evoked potential test and a nerve conduction velocity test may also be performed. An evoked potential test measures the
brain’s activity in response to nerve stimulation. This test can reveal a delayed or impaired response, which is a result of
the demyelination that occurs with MLD. A nerve conduction velocity test is similar to an evoked potential test in that it
measures the speed with which signals travel along nerves. This test, however, does not measure signals in the brain; it
measures electrical signals along the nerves in the arms and legs. A slower-than-normal signal may indicate loss of myelin,
suggesting MLD. Both tests are noninvasive and take about 30 minutes to complete.
Although it is now possible to screen newborns for many genetic diseases using only a drop of blood taken from the infant’s
heel at birth, a newborn screening test for MLD is not available at this time, but is under development.
Finally, molecular analysis, also called DNA testing, can be done to confirm a diagnosis of MLD. In many cases, this kind
of test can even determine which one of the more than 110 MLD-associated alleles is present. This can be useful if the patient
has a family history of MLD.
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