Investigations of micro-organic brain damage (MOBD) in heterozygotes of metachromatic leukodystrophy.
Potential damage of central and peripheral nervous system expressed as micro-organic brain damage (MOBD) was investigated in 27 unrelated heterozygotes with metachromatic leukodystrophy (MLD). Arylsulfatase A (ARSA) was determined in peripheral blood leukocytes and sulfatide excretion was estimated in 24-hour urine collections. Genomic DNA was analyzed for the ARSA pseudodeficiency (PD) allele by a PCR method. Clinical investigations included examination of hyper-reflexia, Babinski reflex, Wechsler Adult Intelligence Scale, Benton test, evoked potentials, and nerve conduction velocity (NCV). In our study, a higher incidence of evident or possible micro-organic brain damage was observed in true MLD/PD and MLD heterozygotes (NO/MLD, where NO means the wild allele) than in controls. On the basis of the Benton test, MOBD was suggested or indicated in 67% of MLD heterozygotes, 50% of MLD/PD heterozygotes, and 26% of controls. In our small group of carriers with MLD and PD mutations, persons NO/MLD(PD) with one wild-type allele did not show MOBD and displayed higher ARSA/beta-galactosidase ratios, unlike true MLD/PD compound heterozygotes who carry MLD-causing mutation in one allele and the ARSA-PD polymorphism in the second. Theoretically, this is a shift from autosomal recessive to autosomal dominant-like inheritance, especially when one cannot exclude the influence of polymorphisms (like ARSA-PD) in the wild allele. Since all psychological tests were age-matched, it can be assumed that the MOBD observed in MLD carriers does not have a progressive character unlike in MLD patients. However, it should be mentioned that MOBD appears to have no overt clinical consequences.
Memorial Institute-Child Health Centre, Department of Metabolic Diseases, Warsaw, Poland.
Anna
A
Tylki-Szymańska
Agnieszka
A
Ługowska
Jolanta
J
Chmielik
Jerzy
J
Kotowicz
Anna
A
Jakubowska-Winecka
Marta
M
Zobel
Johannes
J
Berger
Brunhilde
B
Molzer
D000328:Adult; D001927:Brain Diseases / Q000209:etiology / Q000473:pathology*; D002553:Cerebroside-Sulfatase / Q000097:blood / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D013433:Sulfoglycosphingolipids / Q000652:urine; D001616:beta-Galactosidase / Q000097:blood
D013433:Sulfoglycosphingolipids; D004247:DNA; D002553:Cerebroside-Sulfatase; D001616:beta-Galactosidase