Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cerebroside-Sulfatase”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1975

Metachromatic leukodystrophy. Ultrastructural and enzymatic study of a case of variant O form.

A variant of metachromatic leukodystrophy (MLD), Austin disease, is characterized by a multiple isozyme deficiency of arylsulfatase. A 3 1/2-year-old girl with progressive mental and physical deterioration had decreased activities of arylsulfatases A and B in the leukocytes, shown by acylamide gel electrophoresis. Under the electron microscope, biopsy specimens of the brain and the peripheral nerve showed lamellar structures with socalled zebra bodies in the cytoplasmic processes of glial cells, granulo-membranous inclusions with fingerprint configurations in neurons, and myelinlike material in Schwann cells. Results from our study suggest an intricate nature of this dysmetabolic disorder, which shows ultrastructural changes usually seen in classic MLD, a deficiency of arylsulfatase A only, concomitant with those seen in mucopolysaccharidoses such as Hurler and Sanfilippo syndromes.

Cerebroside-Sulfatase↗
PubMed1978

Monozygotic twins with presumed metachromatic leukodystrophy. Activity of arylsulfatase A in serum of patients and family.

Arylsulfatase A (ASA) activity in urine and serum was assayed on two 21-month-old monozygotic twins with presumed metachromatic leukodystrophy (MLD), their parents, and kin. The patients showed a marked reduction in ASA activity in both urine and serum. The twins' parents and 11 kin, a total of 13 persons, were examined for ASA activity in serum, but it was not possible to delineate heterozygous carriers of MLD by the present study. The assay of ASA activity in serum promises to be useful for diagnosis of MLD.

Cerebroside-Sulfatase↗
PubMed1979

Ocular findings in metachromatic leukodystrophy. An electron microscopic and enzyme study in different clinical and genetic variants.

Histopathological studies of the eyes from three patients affected with the infantile form of metachromatic leukodystrophy (MLD) showed the storage of metachromatic complex lipids in the retinal ganglion cells, in the optic nerve and the ciliary nerves, as well as the storage of a mucopolysaccharide-like material in the nonpigmented epithelium of the ciliary body. The lesions were limited to the optic, ciliary, and sensory nerves in a fourth patient with the juvenile form of the disorder. These morphological aspects, which are probably related to differences in sulfatase A activities, may explain the variability of the ocular manifestations in metachromatic leukodystrophy. Seven children affected with infantile MLD or with mucosulfatidosis were examined by conjunctival biopsy. Typical lesions of the sensory nerves were obvious and allowed the diagnosis of the disease. However, it seemed impossible to separate the different forms by histopathological studies only. The tear enzymes were assayed in most of the cases and demonstrated a profound deficiency of arylsulfatase A, or of arylsulfatase A and B, in the classical MLD and in mucosulfatidosis, respectively.

Cerebroside-Sulfatase↗
PubMed1979

A noninvasive technique for monitoring response to chemotherapy in human acute leukemia.

To see whether urine enzyme activities could be used as an index in evaluating the disease status of leukemia patients, we examined the activities of four enzymes: arylsulfatases A(AS-A) and B(AS-B), alkaline phosphatase (AP), and lactate dehydrogenase (LDH). AP and LDH showed no consistent patterns. The activities of AS-A and AS-B correlated well with the patient's clinical status, increasing during progression of disease and decreasing toward normal activities during responses to therapy, as judged from bone marrow cellularity and differential. Among 23 untreated patients with a histologic diagnosis of acute leukemia we found increased activities of the urine enzymes in these proportions: AS-A in 23 patients (100%), AS-B in 22 (95.7%), AP in 7 (30.4%), and LDH in 10 (43.5%). Five patients in remission from acute leukemia had normal activities for all four enzymes. In one patient in remission for more than one year, a rise in urinary arylsulfatase activity preceded observable bone marrow relapse by 4 months. Unlike that of serum of urine lysozyme and serum copper, the determination of urine arylsulfatase activities appears to be a consistent, useful indicator of response to antileukemic therapy. In contrast to the determination of polyamines, the quantitation of arylsulfatase activity is achieved with greater ease and with instrumentation available in most clinical laboratories.

Alkaline Phosphatase↗
PubMed1979

Sulphatase A: an arylsulphatase and a glycosulphatase.

Sulphatase A was first described as an arylsulphatase but was subsequently shown to have cerebroside sulphatase activity, bydrolysing galactose 3-sulphate residues in certain lipids. A characteristic feature of the arylsulphatase activity is the substrate-induced inactivation of the enzyme which occurs during the catalytic reaction. Present views of the course of this modification are considered. A similar modification of the enzyme does not occur during the cerebroside sulphatase reaction and the fall in velocity noted during most such assays can be explained by disappearance of substrate and accumulation of sulphate. Possible reasons for the difference between the two types of activity are considered. Sulphatase A also hydrolyses hexose sulphates at rates comparable to those of aryl sulphates. The specificity of sulphatase A towards its natural substrates, sulpholipids, is considered in the light of these findings.

Animals↗
PubMed1989

Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy.

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.

Adolescent↗
PubMed1991

Reduced activity of arylsulfatase A and predisposition to neurological disorders: analysis of 140 pediatric patients.

A sample of 140 children exhibiting neurologic disturbances (93 suffering from epilepsy and 47 with delayed psychomotor development or mental retardation) was tested for the activity of some lysosomal enzymes. A partial deficiency of arylsulfatase A (ASA) in leucocytes (activities lower than 60% of the control average) was detected in 36 patients (25.7%), whereas few ASA-deficient individuals (1.4%) were found in the control sample of 71 healthy children. Therefore, the frequency of ASA deficiency is abnormally high in our sample of pediatric patients. ASA activity levels were also assayed on fibroblasts from 12 of the 36 ASA-deficient patients; the mean activity in these cells was 20% of the control average. Excretion of urinary sulfatides was not increased in the tested ASA-deficient patients (10/36). Clinical symptoms of these ASA-deficient patients bore no resemblance to classical metachromatic leucodystrophy (MLD), but resemble literature cases labeled as atypical MLD or diagnostic puzzles. This result suggests that reduced ASA activity might be associated with an increased risk of developing neurologic or neuropsychiatric disturbances in children.

Adolescent↗
PubMed1992

Diagnosis of arylsulfatase A deficiency.

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.

Alleles↗
PubMed1992

Elevated sulfatide excretion in heterozygotes of metachromatic leukodystrophy: dependence on reduction of arylsulfatase A activity.

Sulfatide excretion in urine and arylsulfatase A (ASA) activity in leukocytes were determined in 10 homozygotes of metachromatic leukodystrophy (MLD), 7 obligate and 5 facultative MLD heterozygotes, 6 low ASA subjects (not related to MLD homozygotes), and in 9 controls. As compared to controls (sulfatides: 0-2 nmol/mg lipid; ASA: 101-287 nmol p-nitrocatechol/mg protein/hr), MLD homozygotes displayed highly increased sulfatide excretions (27-280 nmol) and low residual ASA activities (0-13 nmol). Of 12 MLD heterozygotes (ASA: 18-87 nmol) 10 showed increased sulfatides (3-24 nmol). All heterozygotes with ASA activity < 60 nmol (n = 8) had elevated sulfatide excretions (4-24 nmol). Thus, reduction of ASA activity below 40% of the mean value of controls seems to be the critical threshold for elevated sulfatide excretion in MLD heterozygotes. The low ASA subjects (ASA in the heterozygote range) excreted sulfatides in the control range, even those with ASA activities < 60 nmoles (n = 3; including a definite homozygote for ASA-pseudodeficiency; ASA:25 nmol). Statistical evaluation of sulfatide excretion and ASA activity in all subjects (n = 37) revealed a significant inverse relation (Spearman rank correlation; R = 0.8278, P < 0.001). The finding of elevated sulfatide excretion in certain MLD heterozygotes might point to increase of sulfatides also in the nervous system.

Adult↗
PubMed1992

Late-onset metachromatic leukodystrophy: molecular pathology in two siblings.

We report on a new allele at the arylsulfatase A (ARSA) locus causing late-onset metachromatic leukodystrophy (MLD). In that allele arginine84, a residue that is highly conserved in the arylsulfatase gene family, is replaced by glutamine. In contrast to alleles that cause early-onset MLD, the arginine84 to glutamine substitution is associated with some residual ARSA activity. A comparison of genotypes, ARSA activities, and clinical data on 4 individuals carrying the allele of 81 patients with MLD examined, further validates the concept that different degrees of residual ARSA activity are the basis of phenotypical variation in MLD.

Adolescent↗
PubMed1978

The development of lysosomal apparatus. I. Lysosomal enzyme activities in the liver of mice at perinatal stages and those of their mothers.

The enzymatic activity of five acid hydrolases: acid phosphatase, arylsulfatase A, deoxyribonuclease, beta-glucuronidase, and cathepsin D, was assayed in fetal (fifteenth and eighteenth days of pregnancy) and neonatal (Days 0, 5, 10, and 15 post-partum) mouse liver. With the exception of cathepsin D, the activity increased around birth to levels varying according to the enzyme. Histochemical observations of other authors appear to justify, at least in part, the present results, which indicate that late days of fetal development and early neonatal life may constitute a transitional stage to full lysosomal enzyme functionality of the adult organ. The livers of the mothers were also assayed for the same enzymes. Each activity showed a peculiar pattern which was, in turn, different from that found in the liver of the litter for the same enzyme, probably as a cause of the metabolic requirement of the gland. The hypothesis that the lysosomes are heterogeneous in their enzyme composition is suggested by the variety of enzymatic patterns found in the liver of the litters and their mothers.

Acid Phosphatase↗
PubMed1990

Prenatal diagnosis of mucolipidosis type II on first-trimester amniotic fluid.

We investigated the possibility of prenatal diagnosis of mucolipidosis type II (ML II) by lysosomal enzyme determination on amniotic fluid obtained at 11 weeks of gestation in three pregnancies at risk. Diagnosis of ML II was made in one case on the basis of increased levels of five lysosomal enzymes tested. The diagnosis was confirmed on cultured chorionic cells, their cultured medium, 17-week amniotic fluid, and fetal plasma obtained for confirmation prior to the termination of pregnancy.

Adult↗
PubMed1992

Prenatal diagnosis of metabolic diseases on chorionic villi obtained before the ninth week of pregnancy.

Nine pregnancies at risk for various metabolic disorders were monitored by prenatal diagnosis on chorionic villi obtained between the sixth and ninth weeks of pregnancy. A diagnosis of an affected fetus was made in five cases (Sandhoff, Tay-Sachs (2), Pompe's, GM1), while metachromatic leukodystrophy, GM1 (2), and Pompe's were excluded in four cases. It is concluded that chorionic villi are a reliable tissue for prenatal diagnosis of metabolic disorders also when obtained before the ninth week.

Cerebroside-Sulfatase↗
PubMed1978

Studies on the function of the activator of sulphatase A.

The activator of sulphatase A is necessary for the enzymic degradation of sulphatides to cerebrosides at ionic concentrations in the physiological range (1). Activation is probably due to the reversible formation of a one-to-one complex between activator and sulphatides (1,2). Formation of this complex is partly inhibited by cerebrosides due to competitive binding (2), as well as by phospholipids (e.g. lecithin or phosphatidylserine). Inhibition of the complex formation between activator and sulphatides by cerebrosides and phosphatidyl-serine depends on the concentration of the lipids and is of the same order of magnitude as the inhibition (by these lipids) of the enzymic degradation of sulphatides in the presence of activator (1). Moreover the degradation rate of sulphatides increases with the concentration of activator-sulphatide complex in the reaction mixture (1) indicating that the activator-sulphatide complex is the substrate for the enzyme in the degradation of sulphatides by sulphatase A.

Cerebroside-Sulfatase↗