Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

ARSU
8777
Useful For: Detection of metachromatic leukodystrophy
Interpretation: Decreased enzyme levels indicate an individual is affected with metachromatic
leukodystrophy (MLD). Note that individuals with pseudoarylsulfatase A deficiency can have results in
this range, but are otherwise unaffected with MLD. Abnormal results should be confirmed using
ARSU/8777 Arylsulfatase A, Urine. If molecular confirmation is desired, consider molecular genetic
testing of the ARSA gene.
Reference Values:
> or =62 nmol/h/mg
Note: Results from this assay may not reflect carrier status because of individual variation of
arylsulfatase A enzyme levels. Low normal values may be due to the presence of pseudodeficiency gene
or carrier gene. Patients with these depressed levels may be phenotypically normal.
Clinical References: 1. Enns GM, Steiner RD, Cowan TM: Metachromatic leukodystrophy. In
Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoflou, GF Hoffmann, KS
Roth. McGraw-Hill Companies, 2009, pp 742-743 2. von Figura K, Gieselmann V, Jacken J:
Metachromatic leukodystrophy. In The Metabolic and Molecular Basis of Inherited Disease. Vol. 3. 8th
edition. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill Book Company,
2001, pp 3695-3716
Arylsulfatase A, Urine
Clinical Information: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused
by a deficiency of the arylsulfatase A enzyme, which leads to the accumulation of galactosyl sulfatide
(cerebroside sulfate) in the white matter of the central nervous system and in the peripheral nervous
system. Galactosyl sulfatide and, to a smaller extent, lactosyl sulfatide, also accumulate within the kidney,
gallbladder, and other visceral organs and are excreted in excessive amounts in the urine. The 3 clinical
forms of MLD are late-infantile, juvenile, and adult, depending on age of onset. All result in progressive
neurologic changes and leukodystrophy demonstrated on magnetic resonance imaging. Late-infantile
MLD is the most common (50%-60% of cases) and typically presents between age 1 to 2 years with
hypotonia, clumsiness, diminished reflexes, and slurred speech. Progressive neurodegeneration occurs
with a typical disease course of 3 to 10 years. Juvenile MLD (20%-30% of cases) is characterized by
onset between 4 to 14 years. Typical presenting features are behavior problems, declining school
performance, clumsiness, and slurred speech. Neurodegeneration occurs at a somewhat slower and more
variable rate than the late-infantile form. Adult MLD (15%-20% of cases) has an onset after puberty and
can be as late as the fourth or fifth decade. Presenting features are often behavior and personality changes,
including psychiatric symptoms. Clumsiness, neurologic symptoms, and seizures are also common. The
disease course has variable progression and may occur over 2 to 3 decades. The disease prevalence is
estimated to be approximately 1 in 100,000. MLD is an autosomal recessive disorder and is caused by
mutations in the ARSA gene coding for the arylsulfatase A enzyme. This disorder is distinct from
conditions caused by deficiencies of arylsulfatase B (Maroteaux-Lamy disease) and arylsulfatase C
(steroid sulfatase deficiency). Extremely low arylsulfatase A levels have been found in some clinically
normal parents and other relatives of MLD patients. These individuals do not have metachromatic
deposits in peripheral nerve tissues, and their urine content of sulfatide is normal. Individuals with this
"pseudodeficiency" have been recognized with increasing frequency among patients with other apparently
unrelated neurologic conditions as well as among the general population. This has been associated with a
fairly common polymorphism in the ARSA gene which leads to low expression of the enzyme (5%-20%
of normal). These patients can be difficult to differentiate from actual MLD patients. Current treatment
options for MLD are usually focused on managing disease manifestations such as seizures. Bone marrow
transplantation remains controversial, and the effectiveness of enzyme replacement therapy may be
limited due to difficulties crossing the blood-brain barrier. Other treatments under ongoing investigation
include hematopoietic stem cell transplantation and fetal umbilical cord blood transplantation.
Useful For: Detection of metachromatic leukodystrophy as a secondary specimen to confirm results
from leukocytes (preferred initial specimen)
Interpretation: Greatly reduced levels of arylsulfatase A in urine (