Diagnosis of Pseudo-Arylsulfatase A Deficiency with Electrophoretic Techniques

Chang, Patricia L.; Rosa, N. E.; Varey, Peter; Kihara, Hayato; Kolodny, Edwin H.; Davidson, Ronald G.

doi:10.1203/00006450-198418100-00027

Cited by 2 publications

(2 citation statements)

References 2 publications

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“…Urinary ARS A and leukocyte and fibroblast ARS A analyses were performed as described by Baum et al [1959] and modified by Austin et al [1966] with the use of p-nitrocatechol sulfate as substrate. Electrophoretic separation and analysis of ARS isozymes were performed with cellulose acetate electrophoresis according to Rattazzi et al [1973] and Chang et al [1984]. Urinary sulfatide analyses were performed on random samples of urine according to Strasberg et al [1985].…”

Section: Biochemical Studiesmentioning

confidence: 99%

Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy

1989

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In a child with enzymatically and histopathologically proven metachromatic leukodystrophy (MLD), the disease pursued a course typical of juvenile MLD characterized by neurological degeneration beginning at age 9 years and ending in death at age 18. A younger brother of the patient was found to have profound deficiency of arylsulfatase A in leukocytes and to excrete five- to 20-fold greater-than-normal amounts of sulfatide in the urine. He was completely free of symptoms attributable to MLD until age 16 when he developed acute cholecystitis caused by sulfatide accumulation in the gallbladder. Results of detailed neurological examination at age 21 years were normal; formal psychometric assessment showed a full-scale IQ of 105 (Wechsler). Studies on cultured skin fibroblasts from the brother showed defects in arylsulfatase A activity, measured with the use of synthetic and natural substrates, and in radiolabeled sulfatide turnover. Cellulose acetate gel electrophoresis of fibroblast extracts from the patient showed no detectable arylsulfatase A isozyme under conditions that clearly distinguished pseudo-arylsulfatase A deficiency from classical MLD. Biochemically, the patient was indistinguishable from patients with classical MLD; on the other hand, his clinical course is dramatically more benign than that of his sister who was affected with severe MLD.

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Section: Biochemical Studiesmentioning

confidence: 99%

Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy

1989

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“…Enzyme Analyses ARSA was extracted from fibroblast pellets and assayed with the substrate, 4-methylumbelliferyl sulfate [Chang et al, 19811, orp-nitrocatechol sulfate [Baum et al, 19591. It was further separated with electrophoresis on Cellogel before staining with the substrate, 4-methylumbelliferyl sulfate [Rattazzi et al, 19731 as described by Chang et al [1984]. The only modification was that the fibroblast pellets were not sonicated but freeze-thawed 5X before separating the soluble extract from the cell debris.…”

Section: Pedigreesmentioning

confidence: 99%

Diagnosis of arylsulfatase A deficiency

Waye

Chang

1992

Am. J. Med. Genet.

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Metachromatic leukodystrophy (MLD) is a neurologically devastating autosomal recessive disorder in humans associated with deficient arylsulfatase A activity. However, clinically normal individuals described as being pseudo-arylsulfatase-A deficient also demonstrate the same deficiency. Genotypically, they may be homozygous for the pseudodeficiency mutation (associated with 2 A-->G transitions in the cDNA of arylsulfatase A) or heterozygous with one pseudodeficiency and one MLD allele. Using as examples 2 families in which the pseudo deficiency condition occurs either independently or together with MLD, we demonstrate the utility of a proposed diagnostic protocol to provide complete genotype identification of individuals suffering from arylsulfatase A deficiency. Patient fibroblasts are extracted for DNA and a cytoplasmic fraction, which is used for arylsulfatase A enzyme assay. This will identify an arylsulfatase A-deficient group, which is further analyzed electrophoretically. Cells from the clinically affected patients with MLD are completely deficient in arylsulfatase A activity, whereas those from the pseudodeficient individuals demonstrate a characteristic residual arylsulfatase A activity detectable only after electrophoresis. Within this pseudodeficient group, gene amplification of DNA specific for the A-->G mutations will distinguish between those who are homozygous for the pseudodeficiency allele and those who are compound heterozygous for the pseudodeficiency and MLD alleles. This protocol of complete genotype identification requires only about 10(6) fibroblasts (1 x 100 mm dish) and 2 days to complete. Such variant-specific genotype identification increases accuracy and prognostic value of the diagnosis. It will likely become the preferred choice for diagnosis of genetic disease in the future as more variant-specific mutations are identified at the molecular level.

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Diagnosis of Pseudo-Arylsulfatase A Deficiency with Electrophoretic Techniques

Cited by 2 publications

References 2 publications

Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy

Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy

Diagnosis of arylsulfatase A deficiency

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