High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy

Journal Article · Sun Aug 01 00:00:00 EDT 1993 · American Journal of Human Genetics; (United States)

OSTI ID:5852515

Kreysing, J; Bohne, W; Boesenberg, C; Figura, K von; Gieselmann, V ^[1]; Marchesini, S ^[2]; Turpin, J C ^[3]; Baumann, N ^[4]

---

1. Georg August Universitaet, Goettingen (Germany)
2. Univ. of Brescia (Italy)
3. Centre Hospitalier Regional et Universitaire, Reims (France)
4. Hospital de la Salpetriere, Paris (France)

The authors identified a patient suffering from late-infantile metachromatic leukodystrophy (MLD) who has a residual arylsulfatase A (ARSA) activity of about 10%. Fibroblasts of the patient show significant sulfatide degradation activity exceeding that of adult MLD patients. Analysis of the ARSA gene in this patient revealed heterozygosity for two new mutant alleles: in one allele, deletion of C 447 in exon 2 leads to a frameshift and to a premature stop codon at amino acid position 105; in the second allele, a G[yields]A transition in exon 5 causes a Gly[sup 309][yields]Ser substitution. Transient expression of the mutant Ser[sup 309]-ARSA resulted in only 13% enzyme activity of that observed in cells expressing normal ARSA. The mutant ARSA is correctly targeted to the lyosomes but is unstable. These findings are in contrast to previous results showing that the late-infantile type of MLD is always associated with the complete absence of ARSA activity. The expression of the mutant ARSA protein may be influenced by particular features of oligodendrocytes, such that the level of mutant enzymes is lower in these cells than in others. 23 refs., 4 figs., 2 tabs.

• OSTI ID: 5852515
• Journal Information: American Journal of Human Genetics; (United States), Vol. 53:2; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CEREBROSIDES
METABOLISM
ENZYMES
GENE MUTATIONS
LYSOSOMES
METABOLIC DISEASES
MYELIN
NERVE CELLS
NERVE TISSUE
ANIMAL CELLS
ANIMAL TISSUES
BODY
CARBOHYDRATES
CELL CONSTITUENTS
CELL MEMBRANES
DISEASES
GLYCOLIPIDS
LIPIDS
MEMBRANES
MUTATIONS
ORGANIC COMPOUNDS
PROTEINS
SACCHARIDES
SOMATIC CELLS
TISSUES
550400* - Genetics
550900 - Pathology