Ocular movements in lipid storage disease. Reports of juvenile Gaucher disease and the ophthalmoplegic lipidosis.
Explore the source record for details and available documents.
Adolescent↗
SEARCH · PubMed Health
Results for “Gaucher Disease”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Gaucher disease: isolation and comparison of normal and mutant glucocerebrosidase from human spleen tissue.
Glucocerebrosidase was purified 26,000-fold from spleens from normal humans and from patients with Gaucher disease (Gaucher spleens). The specific activities of the purified normal and mutant enzymes with glucocerebroside as substrate were 8.5 X 10(5) and 5.4 X 10(4) nmol/mg of protein per hr, respectively. The ratio of enzymatic activities was constant throughout the isolation procedure. The two enzymes appeared to be similar by other parameters such as substrate affinity, heat lability, and pH optimum. Immunotitration with glucocerebrosidase antiserum showed equivalent quantities of crossreacting material in extracts of normal and Gaucher spleens. These data strongly suggest that the genetic basis of Gaucher disease is a strucutral mutation of glucocerebrosidase. The results of sodium dodecyl sulfate gel electrophporesis also indicate that there are differences between the normal and the Gaucher disease enzyme.
Electrophoresis, Agar Gel↗
Attempt at enzyme replacement in Gaucher disease by renal transplantation.
In Gaucher disease there is a deficiency of the lysosomal enzyme, cerebroside-beta-glucosidase, as a result of which cerebroside (glucosylcereamide) accumulates in various organs. In northern Sweden 22 patients with a juvenile form of this disease have been identified. In one such patient, a girl of 10 years, we have attempted enzyme replacement by renal transplantation. After this operation the hepatic glucocerebroside content fell significantly. In another child afflicted with Gaucher disease in whom splenectomy was performed for severe splenomegaly and hypersplenism there was a progressive increase in the level of this lipid. These findings suggest that enzyme replacement was achieved by transplantation of a normal organ.
Child↗
Clinical variation in 2 related children with neuronopathic Gaucher disease.
The clinical features in 2 second cousins with neuronopathic Gaucher disease include slowly progressive ataxia, spasticity, myoclonus, and seizures with relative preservation of intellectual function. Organomegaly was noted only in Patient 1. Both patients had diffuse slowing with paroxysmal features in electroencephalograms and a deficiency of beta-glucosidase activity in leukocytes and skin fibroblast cultures. The parents of Patient 1 and the related father of Patient 2 had levels of beta-glucosidase activity consistent with the carrier state for Gaucher disease. The value of beta-glucosidase activity in the mother of Patient 2 suggests a different mutation, the result being a defective enzyme component not detectable by measuring total activity.
Child↗
Canine Gaucher disease--the enzymic defect.
beta-Glucosidase activity was investigated in tissues from a case of canine Gaucher disease and from a normal dog. In the latter, enzyme activity showed two pH optima at pH 4-0-4-25 and pH 5-0-5-5. In Gaucher disease tissues, negligible activity could be measured at the mouse acidic pH.
Animals↗
Multiple glycosidase deficiencies in a case of juvenile (type 3) Gaucher disease.
Biochemical investigations were performed on autopsy tissues obtained from an 11-year-old girl who died with the juvenile, subacute neuropathic form of Gaucher disease. In addition to the expected deficiency of glucocerebrosidase activity, extracts of both liver and kidney from this individual displayed a profound (greater than or equal to 90%) deficiency of "soluble" beta-glucosidase, beta-xylosidase, and beta-galactosidase activities. Fibroblasts obtained from this individual also contained markedly reduced levels of beta-xylosidase activity but normal levels of beta-D-fucosidase and beta-galactosidase activity. Because the soluble beta-glucosidase, beta-xylosidase, and a portion of the beta-galactosidase activities from control human liver all cochromatographed on a gel filtration column of Sephadex G-200, it is suggested that these activities all reside in a single enzyme, analogous to the situation described in a number of nonhuman, mammalian tissues. This demonstration of multiple glycosidase deficiencies in addition to the deficiency of glucocerebrosidase in a case of subacute neuropathic Gaucher disease suggests that other biochemical aberrations, in addition to a deficiency of glucocerebrosidase, might contribute to pathology in some cases of Gaucher disease.
Child↗
Gaucher disease in the Afrikaner population of South Africa.
The chronic non-neuropathic form of Gaucher disease has been encountered in 10 individuals in the Afrikaner population of South Africa. The minimum prevalence in this community is 1 in 200 000 with a gene frequency of 0,0022, a heterozygote rate of 0,0044 and at least 9 000 clinically asymptomatic carriers of the abnormal gene. This gene must be present in about 1 in every 220 Afrikaners. The majority of previously reported patients have been Ashkenazi Jews, in whom the condition is relatively benign. By contrast, the disorder in the Afrikaners is precocious in onset, with serious complications and rapid progression. The occurrence of Gaucher disease in a relatively high frequency in the Afrikaner population is important in terms of differential diagnosis, genetic counselling and prevention.
Adolescent↗
The orthopedic aspects of Gaucher disease.
Orthopedic problems are an important feature of the adult, chronic or non-neuropathic form of Gaucher disease. Thirty-five South African patients have been investigated and of these 29 had significant skeletal complications. Twenty-one had nonspecific bone pains, 14 had episodes of pseudoosteomyelitis and 2 had acute hematogenous osteomyelitis. Twenty experienced collapse of femoral heads and in 9, prosthetic joint replacement had been successfully undertaken. Four had kyphoscoliosis due to wedging of vertebral bodies and three had pathological fractures of tubular bones. Twenty-eight of the patients were of Askhenazi Jewish stock and the minimum prevalence of the disorder in this group in South Africa is one in 4,300. If skeletal problems and splenomegally coexist in a Jewish patient, the diagnosis of Gaucher disease warrants serious consideration.
Adolescent↗
Electrophoresis of glucocerebrosidase from normal and Gaucher disease fibroblasts.
A polyacrylamide gel electrophoresis system for glucocerebrosidase has been developed. This method was used to characterize the glucocerebrosidase activity of normal and Gaucher disease fibroblasts; the residual glucocerebrosidase activity in adult Gaucher disease fibroblasts co-migrates with the activity from normal fibroblasts.
Cells, Cultured↗
Non-neuropathic Gaucher disease presenting in infancy.
The non-neuropathic form of Gaucher's disease was diagnosed in 11 children of non-Jewish ancestry in South Africa; all were under the age of 4. None had any neurological involvement and, apart from the precocious presentation and rapid course, the features in each resembled those of the classical 'adult' or chronic non-neuropathic form of Gaucher disease. By contrast, the condition presented after puberty in 24 out of 28 Ashkenazi Jews who were studied during the same investigation. Activity of beta-glucosidase was defective in both groups of patients and they could not be distinguished by histological criteria. Only one child with the infantile neuropathic form of Gaucher disease was identified during the survey. The preponderance of the atypical non-neuropathic form of the disorder in young children is of practical importance from the point of view of differential diagnosis in any child with hepatosplenomegaly.
Age Factors↗
In utero diagnosis of Gaucher disease.
Beta-Glucosidase activity measured by synthetic substrate at pH 4.6 was low in the cultured amniotic cells from two pregnant women at risk for juvenile and adult type Gaucher disease. The diagnosis was confirmed by showing a low activity of beta-glucosidase in the skin fibroblasts with a synthetic substrate or in the spleen with a natural substrate, and by ascertaining the presence of Gaucher cells in the fetal tissues. However, considerable activity of beta-glucosidase measured with synthetic substrate was found in the liver of both affected fetuses and in the spleen of one. It is advisable that the determination of beta-glucosidase to confirm prenatal diagnosis of Gaucher disease be done either in the cultured skin fibroblasts or in the spleen, and if in the spleen, with a natural substrate rather than a synthetic one.
Amniocentesis↗
Properties of beta-glucosidase in cultured skin fibroblasts from controls and patients with Gaucher disease.
Membrane-bound beta-glucosidase from cultured skin fibroblasts can be solubilized in an active form by treatment of membrane preparations with a mixture of Triton X-100 and sodium taurocholate. Several properties of the solubilized enzyme have been studied in fibroblasts from normal, healthy individuals and from 14 patients with different clinical forms of Gaucher disease. The patients studied were classified as follows: group 1 consisted of 10 chronic patients, all (with one exception) of Ashkenazi Jewish origin; group 2 consisted of three black American patients with severe visceral symptoms, manifest from early childhood, but with no apparent neurological involvement; and group 3 consisted of a single white patient with the classical infantile form of the disease. Specific beta-glucosidase activity ranged from 6.6% to 16.5% mean control value in group 1 patients and from 4.1% to 5.8% in groups 2 and 3. When compared with the enzyme from control fibroblasts, the enzyme from chronic Gaucher patients (group 1) was more rapidly inactivated at 50 degrees C, had an altered pH curve, was less effectively inhibited by deoxycorticosterone-beta-glucoside, and was more effectively inhibited by deoxycorticosterone. The enzyme from patients in groups 2 and 3 was qualitatively indistinguishable from the control enzyme in terms of these parameters. No differences in Km (4-methylumbelliferyl-beta-glucoside) or sedimentation coefficient were found between the beta-glucosidases from control and Gaucher cells. The results demonstrate that cells from Ashkenazi Jewish patients with the chronic form of Gaucher disease contain a structurally altered form of beta-glucosidase. This enzyme differs both from normal beta-glucosidase and from the residual enzyme in patients of different ethnic origin and with clinically more severe forms of the disease.
Adolescent↗
Attempt at enzyme replacement by organ transplantation: renal transplantation in Gaucher disease.
Following renal transplantation, hepatic glucocerebroside deposits in a child with Gaucher disease were reduced. This suggests that enzyme replacement had been achieved.
Cadaver↗
Radionuclide assessment of Gaucher's disease.
Gaucher's disease involves multiple organs and may present with variable severity. The scintigraphic appearance of the reticuloendothelial system and bone are described in three patient's with Gaucher's disease. Scintigraphic abnormalities reflected the severity of organ involvement and correlated well with the patients' clinical status. Scintigraphy appears useful for the evaluation and followup of patients with Gaucher's disease.
Adult↗
Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.
BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.
Humans↗
Amyloidosis. An unusual complication of Gaucher's disease.
Gaucher's disease has been associated with plasma cell dyscrasias. A patient had Gaucher's disease, nephrotic syndrome, and systemic amyloidosis. Plasmacytosis in the bone marrow, the presence of light chains in the urine and renal glomeruli, and the finding of low circulating immunoglobulin levels suggest that the amyloid in this patient is related to a plasma cell dyscrasia.
Amyloidosis↗
Gaucher disease in mice induced by conduritol-B-epoxide: morphologic features.
Morphologic changes were studied in mice in which Gaucher disease was induced by the administration of conduritol-B-epoxide. Sixteen newborn Swiss mice received a daily subcutaneous dosage of 100 mg/kg of body weight of conduritol-B-epoxide from one day after birth to 28 days. Light microscopically, no Gaucher cells were noted in the viscera, bone marrow, and the CNS during this study. Ultrastructurally, the spleen and liver showed irregular granules and fibrils in histiocytes and Kupffer cells during the second to fourth week. In the CNS, the neurons showed fibrils and tubular structures within the cisternae of the endoplasmic reticulum at three to four weeks. During the fourth week, they frequently contained well-organized inclusion bodies that were membrane-bound and contained tubular structures that varied from 250 to 500 A in diameter. These inclusion bodies were similar to Gaucher bodies seen in human cases.
Animals↗
Acute neuropathic Gaucher disease in a black infant.
Explore the source record for details and available documents.
Acute Disease↗