Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (432 page)

   
Gene sequence mutation analysis
: >150 mutations in the
ARSA
gene associated with arylsulfatase A deficiency have been reported. Sequencing is expected to detect 97% of ARSA mutations including small deletions, insertions, and inversions within exons.

   
Deletion/duplication analysis
: Gene deletion is rare; no cases of full gene duplication are known. A case of dispermic chimerism has been reported where two ARSA genes were obtained from the father, one with a metachromatic leukodystrophy–causing mutation and the other normal.

   Diagnostic Value

   Absence of ARSA activity in the urine is useful for early diagnosis.

   Keratan sulfate is increased in urine (often two to three times normal).

   Urine sediment may contain metachromatic lipids (from breakdown of myelin products).

   Other Considerations

Biopsy of dental or sural nerve stained with cresyl violet showing accumulation of metachromatic sulfatide is diagnostic; also increased in the brain, kidney, and liver. Pseudoarylsulfatase A deficiency refers to a condition of apparent ARSA enzyme deficiency and cerebroside sulfatase activity in leukocytes in persons without neurologic abnormalities in a metachromatic leukodystrophy family. Conjunctival biopsy shows metachromatic inclusions within Schwann cells.

Suggested Reading

Polten A, Fluharty AL, Fluharty CB, et al. Molecular basis of different forms of metachromatic leukodystrophy.
N Eng J Med.
1991;324:18–22.

MORQUIO SYNDROME (MUCOPOLYSACCHARIDOSIS IVA; GALNS DEFICIENCY)

MIM #253000

   Definition

Morquio syndrome, mucopolysaccharidosis type IVA, is an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate.

   Who Should Be Suspected?

Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal, and there is no direct CNS involvement, although the skeletal changes may result in neurologic complications.

   Relevant Tests and Diagnostic Value

   Enzyme assay in fibroblasts, leukocytes, or amniocytes

   Sequence analysis of the
GALNS
gene (16q24.3)